Identification of M1 muscarinic receptors in pulmonary sympathetic nerves in the guinea-pig by use of pirenzepine.
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-pigs. 2. Pirenzepine was equipotent in the heart and lung as an antagonist of the effects of i.v. ACh at postjunctional muscarinic receptors. Doses of pirenzepine in excess of 1 mumol kg-1 abolished all muscarinic responses consistent with non-selective blockade of M3 receptors on airway smooth muscle and M2 receptors on atrial cells. 3. In the lung, low doses of pirenzepine (1-100 nmol kg-1) increased vagally-induced bronchoconstriction despite concurrent partial blockade of the postjunctional receptors. This suggests blockade of neuronal muscarinic receptors. 4. Propranolol (1 mg kg-1) 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. 5. These 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.
Department of Pharmacology, Royal Free Hospital Medical School, London.
J
J
Maclagan
A D
AD
Fryer
D
D
Faulkner
D000818:Animals; D001980:Bronchi / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism; D010890:Pirenzepine / Q000494:pharmacology*; D011976:Receptors, Muscarinic / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000378:metabolism*; D014630:Vagus Nerve / Q000502:physiology
D011976:Receptors, Muscarinic; D010890:Pirenzepine