Postganglionic muscarinic inhibitory receptors in pulmonary parasympathetic nerves in the guinea‐pig

Faulkner, David; Fryer, A.D.; Maclagan, Jennifer

doi:10.1111/j.1476-5381.1986.tb09485.x

Cited by 71 publications

(40 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There is, at present, no antagonist sufficiently selective to block the neuronal receptors without an action on the postjunctional M3 receptors. However, gallamine and pilocarpine have been shown to act as an antagonist and an agonist respectively, for the prejunctional receptors on pulmonary cholinergic nerves, at doses which are several fold lower than those needed to affect postjunctional muscarinic receptors on airway smooth muscle (Gardier et al, 1974;1978;Fryer & Maclagan, 1984;Faulkner et al, 1986).…”

Section: Effect Ofa Muscarinic Agonistmentioning

confidence: 99%

“…In these species, gallamine was an antagonist for the autoreceptors and caused marked potentiation of vagally-induced bronchoconstriction, whereas the agonist, pilocarpine, inhibited vagally-mediated bronchoconstriction (Faulkner et al, 1986). Using a different experimental approach in vitro, with radiolabelling techniques to measure transmitter release induced by potassium in vitro, Aas & Fonnum (1986) obtained evidence for muscarinic autoreceptors in the pulmonary cholinergic nerves in the albino rat.…”

Section: Introductionmentioning

confidence: 99%

“…Antagonists selective for Ml receptors (pirenzepine) and M2 receptors (methoctramine and gallamine) were used, together with the muscarinic agonist pilocarpine, which has been shown to activate pulmonary prejunctional muscarinic receptors in other species (Fryer & Maclagan, 1984;Faulkner et al, 1986). …”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Evidence for prejunctional M₂ muscarinic receptors in pulmonary cholinergic nerves in the rat

Aas

Maclagan

1990

British J Pharmacology

Self Cite

View full text Add to dashboard Cite

1 The effects of muscarinic antagonists considered to be selective for M1 receptors (pirenzepine) and for M2 receptors (gallamine and methoctramine) were used to investigate the existence of prejunctional muscarinic receptors on cholinergic nerves in the rat lung. The tracheal tube preparation was used in vitro, and contraction of the trachealis muscle was induced by electrical field stimulation (EFS) and by application of an exogenous muscarinic agonist (pilocarpine), and measured as an increase in intraluminal pressure in the tube. 2 The muscarinic antagonists, gallamine and methoctramine, enhanced the contractions induced by nerve stimulation, while contractions elicited by exogenous application of pilocarpine were inhibited by the antagonists. 3 In contrast, pirenzepine blocked contractions induced by both EFS and pilocarpine in a dosedependent manner (EC50 O.1 pM) due to blockade of the postjunctional muscarinic receptors on airway smooth muscle. Potentiation of the response to EFS was never seen with this antagonist. 4 The muscarinic agonist, pilocarpine, caused a slow maintained increase in tone of the tracheal tube and at the same time reduced the contractions induced by EFS. This inhibitory effect was blocked by gallamine and methoctramine. 5 The results suggest that prejunctional inhibitory muscarinic receptors may be localised on the parasympathetic cholinergic nerve terminals innervating tracheal smooth muscle in the rat. This confirms previous findings obtained by measuring transmitter release in this species. The present results suggest that these receptors are of the M2 subtype. Blockade of these autoreceptors with gallamine or methoctramine would increase the output of acetylcholine (ACh) and thereby enhance the nerve-induced contraction of tracheal smooth muscle.

show abstract

Section: Effect Ofa Muscarinic Agonistmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Evidence for prejunctional M₂ muscarinic receptors in pulmonary cholinergic nerves in the rat

Aas

Maclagan

1990

British J Pharmacology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Muscarinic receptors also exist on the post-ganglionic terminals of these cholinergic nerves. These neuronal receptors inhibit transmitter release (Fryer & Maclagan, 1984;1987a;Faulkner et al, 1986) as ipratropium are used clinically as bronchodilators (Fryer & Maclagan, 1987b). As muscarinic antagonists affect both prejunctional and postjunctional muscarinic receptors, the degree of blockade of vagally-induced bronchoconstriction produced by these drugs is dependent on the balance between their pre-and postjunctional blocking activity.…”

Section: Introductionmentioning

confidence: 99%

Identification of M₁ muscarinic receptors in pulmonary sympathetic nerves in the guinea‐pig by use of pirenzepine

Maclagan

Fryer

Faulkner

1989

British J Pharmacology

Self Cite

View full text Add to dashboard Cite

1 The effect of pirenzepine, a muscarinic antagonist considered to be selective for M1 receptors, was studied on bronchoconstriction and bradycardia elicited by preganglionic stimulation of the parasympathetic vagal nerves and by i.v. injections of acetylcholine (ACh) in anaesthetized guinea- 4 Propranolol (1 mg kg-) increased control bronchoconstrictor responses elicited by ACh and vagal stimulation but did not alter the potency of pirenzepine for postjunctional receptors in heart or lung. However, pirenzepine-induced enhancement of vagally-induced bronchoconstriction was abolished by propranolol, suggesting that pirenzepine may be an antagonist for muscarinic receptors located in the sympathetic nerves innervating airway smooth muscle. 5These results confirm that bronchoconstrictor stimuli indirectly initiate activation of an opposing sympathetic reflex in the guinea-pig lung. This response is facilitated by muscarinic receptors located in the sympathetic nervous pathway. 6 The high potency of pirenzepine for the neuronal receptors in the sympathetic nerves suggests that these are M1 receptors. In contrast, the parasympathetic nerves innervating airway smooth muscle in this species contain M2 receptors which inhibit neurotransmission.

show abstract

“…Male Hartley guinea pigs (ϳ400 g) were anesthetized and instrumented in this established model of airway inflation pressure measurements (5,10,14) in protocols previously described (10) and approved by the Columbia University Institutional Animal Care and Use Committee. Anesthesia was induced by intraperitoneal injection of urethane (1.5 g/kg) and increased by 0.5 g ip until lack of foot pinch response before the start of the procedure.…”

Section: Methodsmentioning

confidence: 99%

The GABA_A agonist muscimol attenuates induced airway constriction in guinea pigs in vivo

Gleason¹,

Gallos²,

Zhang³

et al. 2009

Journal of Applied Physiology

View full text Add to dashboard Cite

Gleason NR, Gallos G, Zhang Y, Emala CW. The GABAA agonist muscimol attenuates induced airway constriction in guinea pigs in vivo. J Appl Physiol 106: 1257-1263, 2009. First published February 12, 2009 doi:10.1152/japplphysiol.91314.2008.-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 acetylcholineinduced 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. acetylcholine; histamine; vagal nerve stimulation; gabazine; guanethidine THERE HAS BEEN A GLOBAL INCREASE in the incidence of asthma in the last 20 years (4). Current asthma treatment focuses on avoiding triggers, reducing the incidence of exacerbations, and limiting airway inflammation and chronic remodeling. There have been few new developments in the pharmacological armamentarium against asthma over the last two decades and a paucity of new developments in the treatment of acute airway smooth muscle constriction, which is essential in the treatment of acute exacerbations.Recently, our laboratory identified ␥-aminobutyric acid type A (GABA A ) channels in human and animal airway smooth muscle (12). Activation of GABA A channels in mature central nervous system neurons results in an inward chloride flux resulting in hyperpolarization of the cell membrane (2). In airway smooth muscle, plasma membrane hyperpolarization favors relaxation (11). Although in vitro studies of...

show abstract

Postganglionic muscarinic inhibitory receptors in pulmonary parasympathetic nerves in the guinea‐pig

Cited by 71 publications

References 15 publications

Evidence for prejunctional M₂ muscarinic receptors in pulmonary cholinergic nerves in the rat

Evidence for prejunctional M₂ muscarinic receptors in pulmonary cholinergic nerves in the rat

Identification of M₁ muscarinic receptors in pulmonary sympathetic nerves in the guinea‐pig by use of pirenzepine

The GABA_A agonist muscimol attenuates induced airway constriction in guinea pigs in vivo

Contact Info

Product

Resources

About

Postganglionic muscarinic inhibitory receptors in pulmonary parasympathetic nerves in the guinea‐pig

Cited by 71 publications

References 15 publications

Evidence for prejunctional M2 muscarinic receptors in pulmonary cholinergic nerves in the rat

Evidence for prejunctional M2 muscarinic receptors in pulmonary cholinergic nerves in the rat

Identification of M1 muscarinic receptors in pulmonary sympathetic nerves in the guinea‐pig by use of pirenzepine

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

Contact Info

Product

Resources

About

Evidence for prejunctional M₂ muscarinic receptors in pulmonary cholinergic nerves in the rat

Evidence for prejunctional M₂ muscarinic receptors in pulmonary cholinergic nerves in the rat

Identification of M₁ muscarinic receptors in pulmonary sympathetic nerves in the guinea‐pig by use of pirenzepine

The GABA_A agonist muscimol attenuates induced airway constriction in guinea pigs in vivo