Prejunctional alpha 2-adrenoceptors inhibit acetylcholine release from cholinergic nerves in equine airways

1993 ◽  
Vol 265 (6) ◽  
pp. L565-L570 ◽  
Author(s):  
M. Yu ◽  
Z. Wang ◽  
N. E. Robinson
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Contractile Response ◽  
Electrical Field Stimulation ◽  
Cholinergic Nerves ◽  
Ach Release ◽  
Experimental Conditions ◽  
Adrenoceptor Antagonist ◽  
Cholinergic Neurotransmission ◽  
And Function

To determine the presence and function of alpha 2-adrenoceptors on cholinergic nerves innervating horse airway smooth muscle, the effects of some alpha 2-adrenoceptor agents on contractions of and acetylcholine (ACh) release from equine airway smooth muscle preparations were studied. Muscle contractions were elicited by either electrical field stimulation (EFS) or exogenous ACh. ACh release was induced by EFS and measured by high-pressure liquid chromatography and electrochemical detection. The alpha 2-adrenoceptor agonists clonidine (10(-7) to 10(-5) M) and UK-14,304 (10(-8) to 10(-6) M) concentration dependently inhibited ACh release and the contractile response to EFS but not the response to exogenous ACh. This inhibition was attenuated by the alpha 2-adrenoceptor antagonists yohimbine and idazoxan but not by the alpha 1-adrenoceptor antagonist prazosin. These results indicate that alpha 2-adrenoceptors exist on cholinergic nerves innervating equine airway smooth muscle, and activation of these receptors inhibits cholinergic neurotransmission. The observation that yohimbine alone had little effect on the contractile response to EFS suggests that, under these experimental conditions, endogenous norepinephrine had no influence on tracheal cholinergic neurotransmission via prejunctional alpha 2-adrenoceptors.

Subtypes of muscarinic receptors regulating gallbladder cholinergic contractions

1999 ◽  
Vol 276 (5) ◽  
pp. G1243-G1250 ◽  
Author(s):  
Henry P. Parkman ◽  
Anthony P. Pagano ◽  
James P. Ryan
Keyword(s):  
Smooth Muscle ◽  
Electrical Field Stimulation ◽  
Receptor Subtypes ◽  
Muscarinic Receptor Subtypes ◽  
Cholinergic Nerves ◽  
Ach Release ◽  
Electrical Field ◽  
And Function

The aim of this study was to determine the functional role of muscarinic receptor subtypes regulating gallbladder cholinergic contractions. Electrical field stimulation (EFS; 16 Hz) produced contractile responses of guinea pig gallbladder muscle strips in vitro that were inhibited by 1 μM tetrodotoxin (2 ± 2% of control) and 1 μM atropine (1 ± 1% of control), indicating activation of intrinsic cholinergic nerves. Exogenous ACh (5 μM)-induced contractions were inhibited by atropine (1 ± 1% of control) but not tetrodotoxin (102 ± 1% of control), indicating a direct effect on smooth muscle. The M1 receptor antagonist pirenzepine (10 nM) had no effect on ACh-induced contractions but inhibited EFS-induced contractions by 11 ± 3%. The M2 antagonist methoctramine (10 nM) had no effect on ACh-induced contractions but augmented EFS-induced contractions by 5 ± 2%. The M3 antagonist 4-DAMP (10 nM) inhibited ACh-induced contractions by 14 ± 4% and EFS-induced contractions by 22 ± 5%. In conclusion, specific M1, M2, and M3 receptors modulate gallbladder muscle contractions by regulating ACh release from cholinergic nerves and mediating the contraction. Cholinergic contractions are mediated by M3 receptors directly on the smooth muscle. M2 receptors are on cholinergic nerves and function as prejunctional inhibitory autoreceptors. M1 receptors are on cholinergic nerves and function as prejunctional facilitatory autoreceptors.

Effects of mucosal removal on guinea-pig airway smooth muscle responsiveness

1986 ◽  
Vol 70 (6) ◽  
pp. 571-575 ◽  
Author(s):  
Christopher Murlas
Keyword(s):  
Smooth Muscle ◽  
Guinea Pig ◽  
Airway Smooth Muscle ◽  
Contractile Response ◽  
Electrical Field Stimulation ◽  
Physiological Salt Solution ◽  
Induced Responses ◽  
Field Stimulation ◽  
Electrical Field ◽  
Airway Mucosa

1. The contractile response to histamine, acetylcholine (ACh), KCl or electrical field stimulation (EFS) was examined in paired tracheal rings (one of each being denuded by mucosal rubbing), which were mounted in muscle chambers filled with a continuously aerated physiological salt solution at 37°C. 2. Removal of the respiratory mucosa increased the sensitivity of airway muscle to ACh, histamine and EFS, but not to KCl. The hypersensitivity of denuded rings to histamine and EFS was greater than to ACh. Atropine reduced the histamine hypersensitivity observed. 3. Pretreating intact preparations with indomethacin augmented their responsiveness to EFS, histamine and ACh. 4. Indomethacin augmentation of histamine- and EFS-induced responses was greater in preparations without epithelium. 5. We conclude that the airway mucosa may be associated with a factor that reduces airway smooth muscle responsiveness to stimulation.

SP-induced contraction of airway smooth muscle in normal and allergen-sensitized rabbits: mechanism of action

1995 ◽  
Vol 78 (2) ◽  
pp. 428-432 ◽  
Author(s):  
G. N. Colasurdo ◽  
J. E. Loader ◽  
J. P. Graves ◽  
G. L. Larsen
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Indirect Effects ◽  
Contractile Response ◽  
Complex Interaction ◽  
Direct Effects ◽  
Response Curves ◽  
Cholinergic Neurotransmission ◽  
The Right

We studied the mechanisms involved in the airway smooth muscle (ASM) contraction to substance P (SP) in normal (control) and allergen-sensitized (immune) rabbits as well as immune rabbits exposed to allergen via the airways (immune challenged). Cumulative concentration-response curves to SP (1 x 10(-9) to 1 x 10(-4) M) were performed in ASM segments in the absence and presence of atropine (10(-5) M) in vitro. The maximal contractile response (g tension/g tissue) at 10(-4) M SP and ASM contractions at various concentrations of SP were expressed as means +/- SE. We found no difference in the contractile response to SP between control and immune animals. ASM segments obtained from immune-challenged rabbits were more responsive to SP. Atropine shifted to the right the concentration-response curves and decreased the maximal ASM contraction at 10(-4) M SP in all three groups; this effect, however, was greater in immune-challenged tissues. These findings demonstrate an increased contractile response to SP in immune-challenged animals mediated by a more pronounced facilitation of cholinergic neurotransmission. We conclude that the final ASM response to SP is the result of a complex interaction between direct effects on ASM and indirect effects through modulation of cholinergic neurotransmission.

Pharmacological modulation of cholinergic neurotransmission in guinea pig trachea in vitro

1980 ◽  
Vol 58 (7) ◽  
pp. 810-822 ◽  
Author(s):  
Thomas R. Jones ◽  
John T. Hamilton ◽  
Neville M. Lefcoe
Keyword(s):  
Electrical Stimulation ◽  
Guinea Pig ◽  
Low Frequency ◽  
Electrical Field Stimulation ◽  
Prostaglandin E ◽  
Cholinergic Nerves ◽  
Experimental Conditions ◽  
Cholinergic Neurotransmission ◽  
Stimulation Of

Electrical (field) stimulation of the isolated guinea pig trachea with normal intrinsic tone produced a biphasic response which consisted of an initial (cholinergic) contraction followed by (adrenergic and nonadrenergic) relaxation. Treatment of the tissue with the prostaglandin synthetase inhibitor indomethacin (2.8–5.6 μM) removed intrinsic tone and increased the responsiveness of the tissue to stimulation of cholinergic nerves and to exogenous acetylcholine. Indomethacin-relaxed tracheae were subsequently used to study cholinergic neurotransmission because under these experimental conditions only the contractile component of the response to electrical stimulation was observed. The β adrenoceptor blocking agents dl-propranolol and sotalol and the adrenergic neuron blocking agent guanethidine produced further enhancement of the contraction to electrical stimulation at low frequency (1–10 Hz). Prostaglandin E1, l-noradrenaline, l-adrenaline, salbutamol, phenylephrine, and phentolamine selectively attenuated the contractions to electrical stimulation in concentrations which did not significantly alter the matched responses to exogenous acetylcholine. The selective depressant effect of l-noradrenaline, l-adrenaline, salbutamol, phenylephrine, and phentolamine but not prostaglandin E1 were blocked by dl-propranolol or sotalol. The present results demonstrate that responses to stimulation of cholinergic nerves were altered by (1) prostaglandins and inhibitors of their synthesis, (2) neurally released adrenergic transmitter, and (3) exogenously added β adrenoceptor agonists. The possibility that prostaglandins and adrenergic neurotransmitter may modulate cholinergic neurotransmission at both pre- and post-junctional sites is hypothesized. It is proposed that more attention should be paid to the role of cholinergic transmission and its modulation in the studies of airway smooth muscle.

Beta 2-adrenoceptor activation augments acetylcholine release from tracheal parasympathetic nerves

1995 ◽  
Vol 268 (6) ◽  
pp. L950-L956 ◽  
Author(s):  
X. Y. Zhang ◽  
M. A. Olszewski ◽  
N. E. Robinson
Keyword(s):  
Nitric Oxide ◽  
High Performance ◽  
Contractile Response ◽  
Electrical Field Stimulation ◽  
Ach Release ◽  
Parasympathetic Nerves ◽  
Adrenoceptor Antagonist ◽  
Beta Agonists ◽  
Endogenous Nitric Oxide ◽  
Beta 2

We determined the effects of isoproterenol (Iso) on parasympathetic neurotransmission in isolated equine trachealis strips by comparing the effects of Iso on the contractile response to electrical field stimulation (EFS) and acetylcholine (ACh), as well as by measuring EFS-induced ACh release. The interaction of Iso with muscarinic receptors and endogenous nitric oxide was also investigated. ACh release was measured by high-performance liquid chromatography with electrochemical detection. Iso (10(-7) M or greater) caused significantly more inhibition of EFS- than of ACh-induced contraction, an observation usually interpreted as evidence of prejunctional inhibition of ACh release. However, the latter conclusion was not supported by measurement of ACh release. Iso concentration dependently augmented ACh release, which was reversed by the beta 2-adrenoceptor antagonist ICI-118,551 but not by the beta 1-adrenoceptor antagonist CGP-20,712A. Our results indicate that activation of beta 2-adrenoceptors augments ACh release. Moreover, the comparison of inhibitory effects on EFS- and ACh-induced contraction does not provide correct information about the prejunctional actions of beta-agonists. ACh release was increased more by atropine (10(-7) M) than by Iso (10(-6) M), indicating the predominance of prejunctional inhibitory muscarinic autoreceptors over excitatory beta 2-adrenoceptors. Additionally, we found that inhibition of nitric oxide synthase by NG-nitro-L-arginine did not affect either the cholinergic contractile response or ACh release in both the absence and presence of Iso.

Cholinergic neuromodulation by prostaglandin D2 in canine airway smooth muscle

1987 ◽  
Vol 63 (4) ◽  
pp. 1396-1400 ◽  
Author(s):  
J. Tamaoki ◽  
K. Sekizawa ◽  
P. D. Graf ◽  
J. A. Nadel
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Contractile Response ◽  
Electrical Field Stimulation ◽  
Prostaglandin D2 ◽  
Base Line ◽  
Field Stimulation ◽  
Electrical Field ◽  
Adrenergic Antagonist

To determine whether prostaglandin D2 (PGD2) modulates cholinergic neurotransmission in airway smooth muscle and, if so, what the mechanism of action is, we studied bronchial segments from dogs under isometric conditions in vitro. PGD2 (10(-8)-10(-5) M) elicited dose-dependent muscle contraction, which was reduced after blockade of muscarinic receptors, so that 50% effective dose (ED50) increased from 1.3 +/- 0.3 X 10(-6) to 3.9 +/- 1.0 X 10(-6) M by atropine (10(-6) M) (mean +/- SE, P less than 0.05). Physostigmine, at a concentration insufficient to alter base-line tension (10(-8) M), enhanced the PGD2-induced contraction and decreased ED50 to 6.4 +/- 0.5 X 10(-7) M (P less than 0.05). When added at the highest doses that did not cause spontaneous contraction (1.9 +/- 0.5 X 10(-7) M), PGD2 increased the contractile response to electrical field stimulation (1–50 Hz) by 21.9 +/- 6.6% (P less than 0.001). In contrast to this effect, the response to administered acetylcholine was not affected by PGD2. On the other hand, PGD2-induced augmentation of the response to electrical field stimulation (5 Hz) was further increased from 23.6 +/- 3.0 to 70.4 +/- 8.8% in the presence of physostigmine (10(-8) M) and was abolished by atropine but not affected by the alpha-adrenergic antagonist phentolamine or the histamine H1-blocker pyrilamine. These results suggest that the contraction of airway smooth muscle induced by PGD2 is in in part mediated by a cholinergic action and that PGD2 prejunctionally augments the parasympathetic contractile response, likely involving the accelerated release of acetylcholine at the neuromuscular junction.

Prejunctional inhibitory muscarinic receptors on cholinergic nerves in human and guinea pig airways

1988 ◽  
Vol 64 (6) ◽  
pp. 2532-2537 ◽  
Author(s):  
P. A. Minette ◽  
P. J. Barnes
Keyword(s):  
Guinea Pig ◽  
Muscarinic Receptors ◽  
Contractile Response ◽  
Electrical Field Stimulation ◽  
Cholinergic Nerves ◽  
Ach Release ◽  
Pharmacological Characterization ◽  
Human Airways

We have investigated whether prejunctional inhibitory muscarinic receptors ("autoreceptors") exist on cholinergic nerves in human airways in vitro and whether guinea pig trachea provides a good model for further pharmacological characterization of these receptors. Pilocarpine was used as a selective agonist and gallamine as a selective antagonist of these autoreceptors. Acetylcholine (ACh) release from postganglionic cholinergic nerves was elicited by electrical field stimulation (EFS) (40 V, 0.5 ms, 32 Hz). In human bronchi, pilocarpine inhibited the contractile response to EFS in a dose-related fashion; the dose inhibiting 50% of the control contraction was 2.2 +/- 0.4 x 10(-7) (SE) M (n = 22), and the inhibition was 96% at 3 x 10(-5) M. The inhibitory effects of pilocarpine were antagonized by gallamine in a dose-related fashion. The results were qualitatively the same in the guinea pig. Gallamine significantly enhanced the contractile response to EFS in the guinea pig, whereas pirenzepine failed to do so, which suggests that M2-receptors are involved. We conclude that prejunctional muscarinic receptors that inhibit ACh release are present on cholinergic nerves in human airways and that guinea pig trachea is a good model for further pharmacological characterization of these receptors, which appear to belong to the M2-subtype.

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