scholarly journals Contrasting effects of nitric oxide on food intake and GH secretion stimulated by a GH-releasing peptide

2001 ◽  
pp. 155-162 ◽  
Author(s):  
AE Rigamonti ◽  
SG Cella ◽  
GM Cavallera ◽  
R Deghenghi ◽  
V Locatelli ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Food Intake ◽  
Male Rats ◽  
Acute Administration ◽  
Sprague Dawley ◽  
No Donor ◽  
Gh Secretion ◽  
Combined Administration ◽  
Dual Action ◽  
Plasma Gh

OBJECTIVE: Among the many actions of nitric oxide (NO) are those on endocrine and feeding behaviour. Based on NO involvement in the GH-releasing effect of the GH-releasing peptides (GHRPs) and the reported orexigenic activity of these compounds, we sought to evaluate the effect of the combined administration of a long-acting NO donor, molsidomine, and the newly synthesized GHRP EP92632 on food intake and GH secretion in rats. Moreover, to verify the specificity of a potential NO involvement, we evaluated whether or not the effects of GHRPs were abolished by a pre-treatment with an inhibitor of NO synthase, N-nitro-arginine-methyl-ester (NAME). METHODS: In the food intake experiments, adult Sprague-Dawley male rats underwent acute administration of: (1) EP92632 (160 microg/kg, s.c.); (2) molsidomine (100 mg/kg, i.p.); (3) EP92632+molsidomine; (4) l-NAME (40 and 60 mg/kg, i.p.); (5) EP92632+l-NAME (60 mg/kg, i.p.); (6) EP92632+molsidomine+l-NAME (60 mg/kg, i.p.); and (7) 0.9% saline (0.1 ml/kg, i.p.). After treatments, the cumulative food intake in the 6 post-treatment hours was carefully evaluated. In the neuroendocrine experiments, rats were given the same compounds according to the above reported schedule, except for the use of one dose of NAME (60 mg/kg, i.p.) and a lower EP92632 dose (80 microg/kg, s.c.), and were sampled via atrial cannula. RESULTS: EP92632 significantly stimulated food intake, an effect which was further enhanced by molsidomine, though the latter did not elicit per se any orexigenic effect. l-NAME given alone significantly decreased food intake and abolished the orexigenic effect of the GHRP and the enhancing effect of molsidomine. Plasma GH levels increased significantly following administration of EP92632 but, in contrast to the food intake experiments, molsidomine significantly inhibited both basal and EP92632-stimulated GH secretion; moreover, NAME had a biphasic effect on the EP92632-stimulated GH release: initially inhibitory and then, from 45 min on, stimulatory. NAME did not affect basal GH levels but, surprisingly, combined administration of molsidomine and NAME induced a striking inhibition of both basal and the peptide-stimulated GH release. CONCLUSIONS: In summary, these data indicate that NO in the rat is physiologically involved in a stimulatory way in the GHRP-mediated effect on food intake, but exerts a dual action, probably stimulatory at hypothalamic and inhibitory at pituitary levels, on basal and GHRP-stimulated GH secretion.

scholarly journals Sex and nitric oxide bioavailability interact to modulate interstitial Po2 in healthy rat skeletal muscle

2018 ◽  
Vol 124 (6) ◽  
pp. 1558-1566 ◽  
Author(s):  
Jesse C. Craig ◽  
Trenton D. Colburn ◽  
Daniel M. Hirai ◽  
Michael J. Schettler ◽  
Timothy I. Musch ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Sex Differences ◽  
Male Rats ◽  
Female Rat ◽  
Sprague Dawley ◽  
Rat Skeletal Muscle ◽  
Kinetics Parameters ◽  
No Donor ◽  
No Bioavailability

Premenopausal women express reduced blood pressure and risk of cardiovascular disease relative to age-matched men. This purportedly relates to elevated estrogen levels increasing nitric oxide synthase (NOS) activity and NO-mediated vasorelaxation. We tested the hypotheses that female rat skeletal muscle would: 1) evince a higher O2 delivery-to-utilization ratio (Q̇o2/V̇o2) during contractions; and 2) express greater modulation of Q̇o2/V̇o2 with changes to NO bioavailability compared with male rats. The spinotrapezius muscle of Sprague-Dawley rats (females = 8, males = 8) was surgically exposed and electrically-stimulated (180 s, 1 Hz, 6 V). OxyphorG4 was injected into the muscle and phosphorescence quenching employed to determine the temporal profile of interstitial Po2 (Po2is, determined by Q̇o2/V̇o2). This was performed under three conditions: control (CON), 300 µM sodium nitroprusside (SNP; NO donor), and 1.5 mM Nω-nitro-l-arginine methyl ester (l-NAME; NOS blockade) superfusion. No sex differences were found for the Po2is kinetics parameters in CON or l-NAME ( P > 0.05), but females elicited a lower baseline following SNP (males 42 ± 3 vs. females 36 ± 2 mmHg, P < 0.05). Females had a lower ΔPo2is during contractions following SNP (males 22 ± 3 vs. females 17 ± 2 mmHg, P < 0.05), but there were no sex differences for the temporal response to contractions ( P > 0.05). The total NO effect (SNP minus l-NAME) on Po2is was not different between sexes. However, the spread across both conditions was shifted to a lower absolute range for females (reduced SNP baseline and greater reduction following l-NAME). These data support that females have a greater reliance on basal NO bioavailability and males have a greater responsiveness to exogenous NO and less responsiveness to reduced endogenous NO. NEW & NOTEWORTHY Interstitial Po2 (Po2is; determined by O2 delivery-to-utilization matching) plays an important role for O2 flux into skeletal muscle. We show that both sexes regulate Po2is at similar levels at rest and during skeletal muscle contractions. However, modulating NO bioavailability exposes sex differences in this regulation with females potentially having a greater reliance on basal NO bioavailability and males having a greater responsiveness to exogenous NO and less responsiveness to reduced endogenous NO.

scholarly journals Endogenous Ghrelin Regulates Episodic Growth Hormone (GH) Secretion by Amplifying GH Pulse Amplitude: Evidence from Antagonism of the GH Secretagogue-R1a Receptor

Endocrinology ◽  
2005 ◽  
Vol 146 (9) ◽  
pp. 3836-3842 ◽  
Author(s):  
P. Zizzari ◽  
H. Halem ◽  
J. Taylor ◽  
J. Z. Dong ◽  
R. Datta ◽  
...  
Keyword(s):  
Food Intake ◽  
Area Under The Curve ◽  
Sampling Period ◽  
Pulse Amplitude ◽  
Peak Amplitude ◽  
Male Rats ◽  
Gh Secretion ◽  
Plasma Gh ◽  
Plasma Leptin ◽  
Ghs Receptor

Abstract Ghrelin was purified from rat stomach as an endogenous ligand for the GH secretagogue (GHS) receptor. As a GHS, ghrelin stimulates GH release, but it also has additional activities, including stimulation of appetite and weight gain. Plasma GH and ghrelin secretory patterns appear unrelated, whereas many studies have correlated ghrelin variations with food intake episodes. To evaluate the role of endogenous ghrelin, GH secretion and food intake were monitored in male rats infused sc (6 μg/h during 10 h) or intracerebroventricularly (5 μg/h during 48 h) with BIM-28163, a full competitive antagonist of the GHS-R1a receptor. Subcutaneous BIM-28163 infusion significantly decreased GH area under the curve during a 6-h sampling period by 54% and peak amplitude by 46%. Twelve hours after the end of treatment these parameters returned to normal. Central treatment was similarly effective (−37 and −42% for area under the curve and −44 and −49% for peak amplitude on the first and second days of infusion, respectively). Neither peripheral nor central BIM-28163 injection modified GH peak number, GH nadir, or IGF-I levels. In this protocol, food intake is not strongly modified and water intake is unchanged. Subcutaneous infusion of BIM-28163 did not change plasma leptin and insulin levels evaluated at 1200 and 1600 h. On the contrary, central BIM-28163 infusion slightly increased leptin and significantly increased insulin concentrations. Thus, endogenous ghrelin, through GHS-R1a, acts as a strong endogenous amplifier of spontaneous GH peak amplitude. The mechanisms by which ghrelin modifies food intake remain to be defined and may involve a novel GHS receptor.

scholarly journals Ghrelin Stimulates GH But Not Food Intake in Arcuate Nucleus Ablated Rats

Endocrinology ◽  
2002 ◽  
Vol 143 (9) ◽  
pp. 3268-3275 ◽  
Author(s):  
Hideki Tamura ◽  
Jun Kamegai ◽  
Takako Shimizu ◽  
Shinya Ishii ◽  
Hitoshi Sugihara ◽  
...  
Keyword(s):  
Food Intake ◽  
Normal Control ◽  
Arcuate Nucleus ◽  
Monosodium Glutamate ◽  
Male Rats ◽  
Appetite Control ◽  
Gh Secretion ◽  
Increase Food Intake ◽  
Hypothalamic Arcuate Nucleus ◽  
Plasma Gh

Abstract Ghrelin, an endogenous ligand for the GH secretagogue receptor 1a (GHS-R1a), was originally purified from the rat stomach. Ghrelin mRNA and peptide have also been detected in the hypothalamus and pituitary. Ghrelin is a novel acylated peptide that regulates GH release and energy metabolism. GHS-R1a mRNA is expressed in the pituitary gland as well as in several areas of the brain including the hypothalamus. In this study, we examined whether ghrelin could stimulate GH secretion and feeding in chronic GHRH, neuropeptide Y, and agouti-related protein deficient rats that were neonatally treated with monosodium glutamate (MSG), which destroys the neurons in the hypothalamic arcuate nucleus (ARC). Intravenous (iv) administration of rat ghrelin (10 μg/kg body weight) increased plasma GH levels significantly in the normal adult male rats during a GH trough period of pulsatile GH secretion, while iv injection of ghrelin in MSG-treated rats resulted in a markedly attenuated GH response. When rat ghrelin (10 μg/rat) was administered intracerebroventricular (icv), plasma GH levels were increased comparably in normal control and MSG-treated rats. However, the GH release after icv injection of ghrelin was markedly diminished compared with that after iv administration of a small amount of ghrelin in normal control rats (icv: 10 μg/rat, iv: approximately 4.0 μg/rat), indicating that the GH-releasing activity of exogenous ghrelin is route dependent and at least in part via hypothalamic ARC. The icv administration of 1 μg of ghrelin increased significantly 4-h food intake in normal control, whereas the peptide did not increase food intake in MSG-treated rats, indicating that the feeding response to ghrelin requires intact ARC. Taken together, the primary action of ghrelin on appetite control and GH releasing activity is via the ARC even though it might act on another type of GHS-R besides GHS-R1a.

Maturational changes in the regulation of pulmonary vascular tone by nitric oxide in neonatal rats

2007 ◽  
Vol 293 (5) ◽  
pp. L1261-L1270 ◽  
Author(s):  
Louis G. Chicoine ◽  
Michael L. Paffett ◽  
Mark R. Girton ◽  
Matthew J. Metropoulus ◽  
Mandar S. Joshi ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Guanylyl Cyclase ◽  
Vascular Tone ◽  
Age Groups ◽  
Soluble Guanylyl Cyclase ◽  
No Production ◽  
Sprague Dawley ◽  
No Donor ◽  
Early Postnatal Development ◽  
Old Rats

Nitric oxide (NO) is an important regulator of vasomotor tone in the pulmonary circulation. We tested the hypothesis that the role NO plays in regulating vascular tone changes during early postnatal development. Isolated, perfused lungs from 7- and 14-day-old Sprague-Dawley rats were studied. Baseline total pulmonary vascular resistance (PVR) was not different between age groups. The addition of KCl to the perfusate caused a concentration-dependent increase in PVR that did not differ between age groups. However, the nitric oxide synthase (NOS) inhibitor Nω-nitro-l-arginine augmented the K+-induced increase in PVR in both groups, and the effect was greater in lungs from 14-day-old rats vs. 7-day-old rats. Lung levels of total endothelial, inducible, and neuronal NOS proteins were not different between groups; however, the production rate of exhaled NO was greater in lungs from 14-day-old rats compared with those of 7-day-old rats. Vasodilation to 0.1 μM of the NO donor spermine NONOate was greater in 14-day lungs than in 7-day lungs, and lung levels of both soluble guanylyl cyclase and cGMP were greater at 14 days than at 7 days. Vasodilation to 100 μM of the cGMP analog 8-(4-chlorophenylthio)guanosine-3′,5′-cyclic monophosphate was greater in 7-day lungs than in 14-day lungs. Our results demonstrate that the pulmonary vascular bed depends more on NO production to modulate vascular tone at 14 days than at 7 days of age. The observed differences in NO sensitivity may be due to maturational increases in soluble guanylyl cyclase protein levels.

Abstract P607: Nitric Oxide (NO) Regulates Paracellular Permselectivity in Isolated, Perfused Rat Thick Ascending Limbs through Claudin-19

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Casandra M Monzon ◽  
Jeffrey Garvin
Keyword(s):  
Nitric Oxide ◽  
Control Period ◽  
Sprague Dawley ◽  
Permeability Ratio ◽  
Ionic Selectivity ◽  
No Donor ◽  
Sprague Dawley Rats ◽  
Spermine Nonoate ◽  
Dilution Potential ◽  
Cl Permeability

About 50% of the Na reabsorbed in thick ascending limbs (TALs) traverses the paracellular pathway. The ionic selectivity of this route is regulated by claudins in the tight junctions. TALs express claudin-19 which has been reported to regulate TAL Na permeability. We showed that nitric oxide (NO) decreases Na/Cl permeability ratio (PNa/PCl) in TALs by increasing the absolute permeabilities of both ions though PCl increased more. However, whether NO affects paracellular permeability via claudin-19 is unknown. We hypothesize that NO regulates the paracellular permselectivity in TALs through this claudin. To test this we perfused TALs from Sprague Dawley rats and measured dilution potentials (a measure of permselectivity) with and without exogenously-added or endogenously-produced NO in the presence or absence of an antibody against an extracellular domain of claudin-19 or Tamm-Horsfall protein (control). Dilution potentials were generated by reducing bath NaCl from 141 to 32 mM. For the NO donor spermine NONOate (SPM): during the control period, the dilution potential was -9.3 ± 1.8 mV. After SPM (200 μM), it was -6.7 ± 1.6 mV (n = 6; p < 0.003). In the presence of the claudin-19 antibody, SPM had no significant effect on dilution potentials (claudin-19 antibody alone: -12.7 ± 2.1 mV vs claudin-19 antibody + SPM: -12.9 ± 2.4 mV; n = 6). The claudin-19 antibody alone had no effect on dilution potentials. In the presence of the Tamm-Horsfall protein, the effect of SPM was still present (Tamm-Horsfall protein antibody alone: -9.7 ± 1.0 mV; Tamm-Horsfall protein antibody + SPM: -6.3 ± 1.1 mV, p<0.006, n = 6). For experiments with endogenously-produced NO, L-arginine the substrate for NO synthase was added. During the control period, the dilution potential was -11.0 ± 1.1 mV. After L-arginine (500 μM) treatment, they were -9.0 ± 1.2 mV (n = 9; p < 0.05). In the presence of the claudin-19 antibody, L-arginine had no significant effect on dilution potentials (claudin-19 antibody alone: -10.1 ± 0.9 mV vs claudin-19 antibody + L-arginine: -10.1 ± 1.0 mV; n = 9). In the presence of the Tamm-Horsfall protein, the effect of L-arginine was still present. We conclude that the actions of NO on the paracellular permselectivity in thick ascending limbs are at least in part mediated by claudin-19.

Effects of androgens on bioactivity and immunoreactivity of pituitary FSH in GnRH antagonist-treated male rats

1990 ◽  
Vol 122 (2) ◽  
pp. 168-174 ◽  
Author(s):  
Om P. Sharma ◽  
Shafiq A. Khan ◽  
Gerhard F. Weinbauer ◽  
Mohammed Arslan ◽  
Eberhard Nieschlag
Keyword(s):  
Isoelectric Focusing ◽  
Gnrh Antagonist ◽  
Molecular Composition ◽  
Male Rats ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Combined Administration ◽  
Ph Range ◽  
Fsh Bioactivity

Abstract The effects of androgens on the bioactivity and molecular composition of pituitary FSH were examined in intact and GnRH antagonist-suppressed male rats. Eight groups of adult Sprague-Dawley rats were subjected to the following treatments: antagonist (75 μg/day by osmotic minipumps; sc), testosterone-filled Silastic implants (3×5 cm, sc), dihydrotestosterone-filled Silastic implants (3×5 cm, sc), E2 benzoate (15 μg/day, sc), and combined administration of antagonist with either steroid for 3 weeks. At the end of the treatment period, pituitaries were dissected out and homogenised. FSH content was determined in the pituitary extracts by an in vitro bioassay and a radioimmunoassay. Individual pituitary extracts from rats treated with vehicle, testosterone and testosterone + antagonist were subjected to isoelectric-focusing on sucrose density gradients performed in the pH range from 3.5 to 7.0. Individual isoelectric-focusing fractions (100-120) were analysed for bioactive and immunoreactive FSH. Treatment with antagonist, E2 or antagonist + E2 caused a significant decrease in pituitary FSH, whereas testosterone and dihydrotesterone alone or in combination with antagonist prevented the decrease in pituitary FSH. The effects of all treatments on both bioactive and immunoreactive FSH were similar. Testosterone treatment not only maintained FSH synthesis but also altered the molecular composition of pituitary FSH. Following treatment with testosterone there was a shift of maximal FSH bioactivity to the more acidic pH range. On the other hand, less bioactivity was recovered than corresponding immunoreactivity in the higher pH region, resulting in significantly reduced ratios of bioactivity to immunoreactivity of FSH. No significant differences were found in the isoelectric-focusing profiles or bioactivity to immunoreactivity ratios of pituitary FSH in animals treated with testosterone alone or in combination with antagonist. The results demonstrate that testosterone not only maintained the synthesis of both bioactive and immunoreactive FSH in male rats, but also influences the molecular composition of pituitary FSH. These effects of testosterone on pituitary FSH appear not to be mediated through hypothalamic GnRH.

Mechanism of action of Hexarelin. I. Growth hormone-releasing activity in the rat

1996 ◽  
Vol 135 (4) ◽  
pp. 481-488 ◽  
Author(s):  
Antonio Torsello ◽  
Roberta Grilli ◽  
Marina Luoni ◽  
Margherita Guidi ◽  
Maria Cristina Ghigo ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Mechanism Of Action ◽  
Direct Action ◽  
Male Rats ◽  
Surgical Ablation ◽  
Adult Rats ◽  
Gh Secretion ◽  
Plasma Gh

Torsello A, Grilli R, Luoni M, Guidi M, Ghigo MC, Wehrenberg WB, Deghenghi R, Müller EE, Locatelli V. Mechanism of action of Hexarelin. I. Growth hormone-releasing activity in the rat. Eur J Endocrinol 1996;135:481–8. ISSN 0804–4643 We have reported Hexarelin (HEXA), an analog of growth hormone-releasing peptide 6 (GHRP-6), potently stimulates growth hormone (GH) secretion in infant and adult rats. This study was undertaken to further investigate Hexarelin's mechanisms of action. In 10-day-old pups, treatments with HEXA (80 μg/kg, b.i.d.) for 3–10 days significantly enhanced, in a time-related fashion, the GH response to an acute HEXA challenge. Qualitatively similar effects were elicited in pups passively immunized against growth hormone-releasing hormone (GHRH) from birth. In adult male rats, a 5-day pretreatment with HEXA (150 μg/kg, b.i.d.) did not enhance the effect of the acute challenge, and the same pattern was present after a 5-day pretreatment in male rats with surgical ablation of the mediobasal hypothalamus (MBH-ablated rats). In addition, in adult sham-operated rats, Hexarelin (300 μg/kg, iv) induced a GH response greater (p < 0.05) than that induced by GHRH (2 μg/kg, iv). However, in MBH-ablated rats 7 days after surgery, GHRH was significantly (p < 0.05) more effective than HEXA, and 30 days after surgery HEXA and GHRH evoked similar rises of plasma GH. Finally, the in vitro Hexarelin (10−6 mol/l) effect was transient while GHRH (10−8 mol/l) induced a longer lasting and greater GH release. Three different mechanisms, not mutually exclusive, are postulated for Hexarelin stimulation of GH secretion in vivo: a direct action on the pituitary, though of minor relevance; an indirect action that involves release of GHRH, of relevance only in adult rats; and an action through the release of a still unknown hypothalamic "factor", which in infant and adult rats elicits GH release acting sinergistically with GHRH. Antonio Torsello, Department of Pharmacology, via Vanvitelli 32, 20129 Milano, Italy

scholarly journals GH and cortisol rebound rise during and following a somatostatin infusion: studies in dogs with the use of a GH-releasing peptide

2002 ◽  
Vol 174 (3) ◽  
pp. 387-394 ◽  
Author(s):  
AE Rigamonti ◽  
SM Bonomo ◽  
SG Cella ◽  
EE Muller
Keyword(s):  
Hpa Axis ◽  
Plasma Cortisol ◽  
Cortisol Response ◽  
Marked Rise ◽  
Releasing Hormone ◽  
Gh Secretion ◽  
Combined Administration ◽  
Cortisol Responses ◽  
Plasma Gh

GH-releasing peptides (GHRPs), a class of small synthetic peptide and non-peptide compounds, act on specific receptors at both the pituitary and the hypothalamic level to stimulate GH release in both humans and other animals. GHRPs, like corticotropin-releasing hormone (CRH), also possess acute ACTH- and cortisol-releasing activity, although the mechanisms underlying the stimulatory effect of GHRPs on the hypothalamo-pituitary-adrenal (HPA) axis are still unclear. In recent years, studies in humans and other animals have provided evidence that the rebound GH rise which follows withdrawal of an infusion of somatostatin (SS) (SSIW) is due, at least in part, to the functional activation of GH-releasing hormone (GHRH) neurons of the recipient organism. Unexpectedly, in humans, SS infusion, at a dose inhibiting basal GH secretion, has been associated with an activation of the HPA axis, leading to the hypothesis that this response was mediated, at least in part, by a central nervous system ACTH-releasing mechanism activated by the SS-induced decrease in GH secretion. Interestingly, the rebound GH rise which follows SSIW was magnified by the administration, before SS withdrawal, of a GHRP, implying that the SSIW approach could also be exploited to investigate in vivo the functional interaction in the process of GH and/or ACTH/cortisol secretion between endogenous GHRH (and/or other ACTH-releasing mechanisms) and GHRPs. In the present study, six young beagle dogs were given, on different occasions, at the beginning and at the end of a 3-h i.v. infusion of SS or saline (SAL), a bolus of physiological SAL or a GHRP compound, EP51216. SSIW induced a GH rebound rise without affecting plasma cortisol concentrations, while the withdrawal of SAL infusion was ineffective on either hormone paradigm. Administration of EP51216 at the beginning of SAL infusion evoked release of both GH and cortisol, whereas EP51216 administration at the withdrawal of SAL infusion evoked somatotroph and cortisol responses which were reduced in amplitude and duration. SS infusion significantly reduced the secretion of GH elicited by EP51216 but did not affect the rise of plasma cortisol levels. Interestingly, SSIW resulted in a marked enhancement of the somatotroph and cortisol responses evoked by EP51216. The marked rise of plasma GH levels induced by the GHRP after SSIW recalled that occurring after acute combined administration of recombinant human GHRH and EP51216, implying that exogenously delivered GHRP had synergized with the endogenous GHRH release triggered by SSIW. In contrast, acute combined administration of GHRH and the GHRP induced a cortisol response not different from that induced by GHRP alone, indicating that endogenous GHRH release was not involved in the enhanced cortisol response following EP51216 administration after SSIW. Similarly, the direct involvement of endogenous CRH could be ruled out, since i.v. administration of ovine CRH after SSIW evoked cortisol peak levels not different from those evoked by CRH at the withdrawal of SAL infusion. In conclusion, enhancement of the GH response to EP51216 alone by SSIW, to an extent reminiscent of that following combined administration of GHRH and EP61216, reinforces the view that SSIW elicits release of endogenous GHRH. Further studies are indeed necessary for a better understanding of the mechanisms underlying the enhanced cortisol response, since from now on the involvement of endogenous GHRH or CRH can be ruled out.

scholarly journals Obestatin Partially Affects Ghrelin Stimulation of Food Intake and Growth Hormone Secretion in Rodents

Endocrinology ◽  
2007 ◽  
Vol 148 (4) ◽  
pp. 1648-1653 ◽  
Author(s):  
Philippe Zizzari ◽  
Romaine Longchamps ◽  
Jacques Epelbaum ◽  
Marie Thérèse Bluet-Pajot
Keyword(s):  
Food Intake ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Male Rats ◽  
Pituitary Cells ◽  
Gh Secretion ◽  
Freely Moving ◽  
Stimulation Of

Administration of ghrelin, an endogenous ligand for the GH secretagogue receptor 1a (GHSR 1a), induces potent stimulating effects on GH secretion and food intake. However, more than 7 yr after its discovery, the role of endogenous ghrelin remains elusive. Recently, a second peptide, obestatin, also generated from proteolytic cleavage of preproghrelin has been identified. This peptide inhibits food intake and gastrointestinal motility but does not modify in vitro GH release from pituitary cells. In this study, we have reinvestigated obestatin functions by measuring plasma ghrelin and obestatin levels in a period of spontaneous feeding in ad libitum-fed and 24-h fasted mice. Whereas fasting resulted in elevated ghrelin levels, obestatin levels were significantly reduced. Exogenous obestatin per se did not modify food intake in fasted and fed mice. However, it inhibited ghrelin orexigenic effect that were evident in fed mice only. The effects of obestatin on GH secretion were monitored in superfused pituitary explants and in freely moving rats. Obestatin was only effective in vivo to inhibit ghrelin stimulation of GH levels. Finally, the relationship between octanoylated ghrelin, obestatin, and GH secretions was evaluated by iterative blood sampling every 20 min during 6 h in freely moving adult male rats. The half-life of exogenous obestatin (10 μg iv) in plasma was about 22 min. Plasma obestatin levels exhibited an ultradian pulsatility with a frequency slightly lower than octanoylated ghrelin and GH. Ghrelin and obestatin levels were not strictly correlated. In conclusion, these results show that obestatin, like ghrelin, is secreted in a pulsatile manner and that in some conditions; obestatin can modulate exogenous ghrelin action. It remains to be determined whether obestatin modulates endogenous ghrelin actions.

scholarly journals The Effect of Mitochondrial Complex I-Linked Respiration by Isoflurane Is Independent of Mitochondrial Nitric Oxide Production

2018 ◽  
Vol 8 (2) ◽  
pp. 113-122 ◽  
Author(s):  
Fuqi Xu ◽  
Shigang Qiao ◽  
Hua Li ◽  
Yanjun Deng ◽  
Chen Wang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Mitochondrial Respiration ◽  
Complex I ◽  
Adenosine Diphosphate ◽  
Sprague Dawley ◽  
No Donor ◽  
Anesthetic Preconditioning ◽  
Rat Hearts ◽  
Nos Inhibitor

Background: Anesthetic preconditioning (APC) of the myocardium is mediated in part by reversible alteration of mitochondrial function. Nitric oxide (NO) inhibits mitochondrial respiration and may mediate APC-induced cardioprotection. In this study, the effects of isoflurane on different states of mitochondrial respiration during the oxidation of complex I-linked substrates and the role of NO were investigated. Methods: Mitochondria were isolated from Sprague-Dawley rat hearts. Respiration rates were measured polarographically at 28ºC with a computer-controlled Clark-type O2 electrode in the mitochondria (0.5 mg/mL) with complex I substrates glutamate/malate (5 mM). Isoflurane (0.25 mM) was administered before or after adenosine diphosphate (ADP)-initiated state 3 respiration. The NO synthase (NOS) inhibitor L-N5-(1-iminoethyl)-ornithine (L-NIO, 10 μM) and the NO donor S-nitroso-N-acetylpenicillamine (SNAP, 1 μM) were added before or after the addition of ADP. Results: Isoflurane administered in state 2 increased state 2 respiration and decreased state 3 respiration. This attenuation of state 3 respiration by isoflurane was similar when it was given during state 3. L-NIO did not alter mitochondrial respiration or the effect of isoflurane. SNAP only, added in state 3, decreased state 3 respiration and enhanced the isoflurane-induced attenuation of state 3 respiration. Conclusion: Isoflurane has clearly distinguishable effects on different states of mitochondrial respiration during the oxidation of complex I substrates. The uncoupling effect during state 2 respiration and the attenuation of state 3 respiration may contribute to the mechanism of APC-induced cardioprotection. These effects of isoflurane do not depend on endogenous mitochondrial NO, as the NOS inhibitor L-NIO did not alter the effects of isoflurane on mitochondrial respiration.

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