Direct and indirect actions of histamine on airway smooth muscle in guinea pigs

1984 ◽  
Vol 62 (6) ◽  
pp. 727-733 ◽  
Author(s):  
D. F. Biggs
Keyword(s):  
Smooth Muscle ◽  
Sodium Cromoglycate ◽  
Airway Smooth Muscle ◽  
Muscarinic Receptors ◽  
Guinea Pigs ◽  
The Other ◽  
Glossopharyngeal Nerve ◽  
Drug Induced ◽  
Afferent Pathways

Studies in guinea pigs showed that some forms of drug-induced bronchospasm are reflexogenic involving afferents in the glossopharyngeal nerve. At least two pathways appear to be involved. One pathway contains H1 receptors and is blocked by mepyramine and sodium cromoglycate (SCG), and its pharmacological characteristics are similar to those of active reflex vasodilation. The other appears to involve peripheral muscarinic receptors. The findings also indicate that SCG may act on efferent as well as afferent pathways.

Bronchopulmonary inflammation and airway smooth muscle hyperresponsiveness induced by nitrogen dioxide in guinea pigs

1999 ◽  
Vol 374 (2) ◽  
pp. 241-247 ◽  
Author(s):  
Alberto Papi ◽  
Silvia Amadesi ◽  
Pasquale Chitano ◽  
Piera Boschetto ◽  
Adalberto Ciaccia ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Nitrogen Dioxide ◽  
Airway Smooth Muscle ◽  
Guinea Pigs

Racemic salbutamol administration to guinea-pigs selectively augments airway smooth muscle responsiveness to cholinoceptor agonists

2001 ◽  
Vol 21 (4) ◽  
pp. 211-217 ◽  
Author(s):  
James R. Loss ◽  
Rick S. Hock ◽  
Stephen G. Farmer ◽  
Raymond F. Orzechowski
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Guinea Pigs

scholarly journals The GABAA agonist muscimol attenuates induced airway constriction in guinea pigs in vivo

2009 ◽  
Vol 106 (4) ◽  
pp. 1257-1263 ◽  
Author(s):  
Neil R. Gleason ◽  
George Gallos ◽  
Yi Zhang ◽  
Charles W. Emala
Keyword(s):  
Smooth Muscle ◽  
Cell Membrane ◽  
Airway Smooth Muscle ◽  
Guinea Pigs ◽  
Neural Control ◽  
Chronic Obstructive ◽  
Airway Smooth Muscle Cells ◽  
Membrane Hyperpolarization ◽  
Airway Constriction

GABAA channels are ubiquitously expressed on neuronal cells and act via an inward chloride current to hyperpolarize the cell membrane of mature neurons. Expression and function of GABAA channels on airway smooth muscle cells has been demonstrated in vitro. Airway smooth muscle cell membrane hyperpolarization contributes to relaxation. We hypothesized that muscimol, a selective GABAA agonist, could act on endogenous GABAA channels expressed on airway smooth muscle to attenuate induced increases in airway pressures in anesthetized guinea pigs in vivo. In an effort to localize muscimol's effect to GABAA channels expressed on airway smooth muscle, we pretreated guinea pigs with a selective GABAA antagonist (gabazine) or eliminated lung neural control from central parasympathetic, sympathetic, and nonadrenergic, noncholinergic (NANC) nerves before muscimol treatment. Pretreatment with intravenous muscimol alone attenuated intravenous histamine-, intravenous acetylcholine-, or vagal nerve-stimulated increases in peak pulmonary inflation pressure. Pretreatment with the GABAA antagonist gabazine blocked muscimol's effect. After the elimination of neural input to airway tone by central parasympathetic nerves, peripheral sympathetic nerves, and NANC nerves, intravenous muscimol retained its ability to block intravenous acetylcholine-induced increases in peak pulmonary inflation pressures. These findings demonstrate that the GABAA agonist muscimol acting specifically via GABAA channel activation attenuates airway constriction independently of neural contributions. These findings suggest that therapeutics directed at the airway smooth muscle GABAA channel may be a novel therapy for airway constriction following airway irritation and possibly more broadly in diseases such as asthma and chronic obstructive pulmonary disease.

G protein-coupled receptor kinase 5 regulates airway responses induced by muscarinic receptor activation

2004 ◽  
Vol 286 (2) ◽  
pp. L312-L319 ◽  
Author(s):  
J. K. L. Walker ◽  
R. R. Gainetdinov ◽  
D. S. Feldman ◽  
P. K. McFawn ◽  
M. G. Caron ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
G Protein ◽  
Muscarinic Receptor ◽  
Airway Smooth Muscle ◽  
Muscarinic Receptors ◽  
Muscle Relaxation ◽  
Receptor Activation ◽  
Smooth Muscle Relaxation ◽  
Airway Responses ◽  
G Protein Coupled

G protein-coupled receptors (GPCRs) transduce extracellular signals into intracellular events. The waning responsiveness of GPCRs in the face of persistent agonist stimulation, or desensitization, is a necessary event that ensures physiological homeostasis. GPCR kinases (GRKs) are important regulators of GPCR desensitization. GRK5, one member of the GRK family, desensitizes central M2 muscarinic receptors in mice. We questioned whether GRK5 might also be an important regulator of peripheral muscarinic receptor responsiveness in the cardiopulmonary system. Specifically, we wanted to determine the role of GRK5 in regulating muscarinic receptor-mediated control of airway smooth muscle tone or regulation of cholinergic-induced bradycardia. Tracheal pressure, heart rate, and tracheal smooth muscle tension were measured in mice having a targeted deletion of the GRK5 gene ( GRK5- /-) and littermate wild-type (WT) control mice. Both in vivo and in vitro results showed that the airway contractile response to a muscarinic receptor agonist was not different between GRK5- /- and WT mice. However, the relaxation component of bilateral vagal stimulation and the airway smooth muscle relaxation resulting from β2-adrenergic receptor activation were diminished in GRK5- /- mice. These data suggest that M2 muscarinic receptor-mediated opposition of airway smooth muscle relaxation is regulated by GRK5 and is, therefore, excessive in GRK5- /- mice. In addition, this study shows that GRK5 regulates pulmonary responses in a tissue- and receptor-specific manner but does not regulate peripheral cardiac muscarinic receptors. GRK5 regulation of airway responses may have implications in obstructive airway diseases such as asthma or chronic obstructive pulmonary disease.

Muscarinic receptor reserve of airway smooth muscle and the response to isoproterenol

1990 ◽  
Vol 68 (3) ◽  
pp. 1017-1023
Author(s):  
J. M. Madison
Keyword(s):  
Smooth Muscle ◽  
Muscarinic Receptor ◽  
Airway Smooth Muscle ◽  
Muscarinic Receptors ◽  
Important Determinant ◽  
Effective Concentration ◽  
Tracheal Smooth Muscle ◽  
Receptor Reserve ◽  
Force Transducers

It has been hypothesized that the muscarinic receptor reserve for contraction of airway smooth muscle is an important determinant of the potency with which isoproterenol relaxes submaximal muscarinic contractions. The goals of this study were to inactivate, with phenoxybenzamine, a fraction of the muscarinic receptors present in canine tracheal smooth muscle, and then to determine whether this decrease in muscarinic receptor reserve altered the potency with which isoproterenol relaxed submaximal muscarinic contractions. Strips of smooth muscle were suspended from force transducers in vitro and preincubated with either vehicle (untreated) or phenoxybenzamine (10(-5) M) for 30 min. For muscarinic contractions induced by carbachol that were approximately 70-80% of maximum, the half-maximally effective concentration of isoproterenol was 2.4 +/- 0.8 x 10(-7) M for untreated strips but 5.8 +/- 1.3 x 10(-9) M for strips treated with phenoxybenzamine (n = 6, P less than 0.05). We concluded that treatment with phenoxybenzamine increased the sensitivity of a submaximal muscarinic contraction to isoproterenol. The results support the hypothesis that the muscarinic receptor reserve for contraction is an important determinant of the potency with which isoproterenol relaxes submaximal muscarinic contractions.

Release of epithelium-derived relaxing factor after ozone inhalation in dogs

1988 ◽  
Vol 65 (3) ◽  
pp. 1238-1243 ◽  
Author(s):  
G. L. Jones ◽  
C. G. Lane ◽  
E. E. Daniel ◽  
P. M. O'Byrne
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Airway Epithelium ◽  
Airway Hyperresponsiveness ◽  
The Other ◽  
Tracheal Epithelium ◽  
Control Group ◽  
Relaxing Factor

Airway epithelium has been reported to release epithelium-derived relaxing factor (EpDRF), which inhibits contraction of airway smooth muscle. This study tested the hypothesis that airway hyperresponsiveness after inhalation of ozone in dogs results from an inability to produce EpDRF. Two groups of five dogs each were studied; one group inhaled ozone, the other dry room air. Ozone-treated dogs developed airway hyperresponsiveness, whereas the control group did not. The acetylcholine provocative concentration decreased from 4.17 (%SE 1.35) to 0.56 mg/ml (%SE 1.24) (P = 0.0006) in the ozone-treated dogs and was 18.76 (%SE 2.04) and 29.77 mg/ml (%SE 2.07) in the air-treated dogs (P = 0.47). In vitro the presence of airway epithelium reduced the constrictor responses to acetylcholine, histamine, serotonin, and KCl in trachealis strips from the control dogs. This effect of epithelium was still present in trachealis strips from dogs with airway hyperresponsiveness. These results demonstrate that EpDRF is released from canine tracheal epithelium, that this function is not impaired in dogs with airway hyperresponsiveness after inhaled ozone, and that loss of EpDRF is not responsible for the development of airway hyperresponsiveness after inhaled ozone in dogs.

Sign in / Sign up

Export Citation Format

Share Document