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

Abstract

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.

Effect of pirenzepine and gallamine on cardiac and pulmonary muscarinic receptors in the rabbit

“…Thus, it is unlikely that sympathetic reflex responses to the lung were elicited by either stimulus. This contrasts with results obtained in the anaesthetized guinea-pig, where bronchoconstrictor stimuli are increased by propranolol due to blockade of a sympathetic bronchodilator reflex (McCulloch et al, 1967;Maclagan et al, 1989). The lack of a sympathetic bronchodilator reflex in the rabbit may be due to the effects of the general anaesthetic or to the absence of a sympathetic innervation of airway smooth muscle in that species (Mann, 1971).…”

“…Figure 3 and the 5 I bronchoconstriction due to blockade of neuronal receptors (Fryer & Maclagan, 1984;Maclagan et al, 1989).…”

“…In the lung in the guinea-pig, the sympathetic nerves innervating airway smooth muscle contain Ml receptors that facilitate transmission (Maclagan et al, 1989) but this mechanism has not yet been demonstrated in the lung in any other species. On the other hand, the parasympathetic nerves innervating the lung have been demonstrated to contain M2 receptors in several species.…”

“…Bronchoconstriction was recorded (as described by Maclagan et al, 1989) as an increase in pulmonary inflation pressure (Ppi) over the basal insufflation pressure change produced by the pump. The experiments were repeated in a second group of animals which received propranolol (1 mg kg 1, i.v.)…”

Polymorphisms in the Muscarinic Receptor 1 Gene Confer Susceptibility to Asthma in Japanese Subjects

“…An M1 receptordependent pathway counteracts cholinergic bronchoconstriction, possibly via the release of a relaxing agent (8); both respiratory epithelia and sympathetic nerve terminals within bronchial smooth muscle are equipped with M1 receptors (7,26) and releasable bronchodilating agents, such as nitric oxide and prostaglandin E 2 (27). Studies with the M1 receptor-preferring antagonist, pirenzepine, have also suggested the existence of pulmonary M1 receptors modulating airway diameter (28).…”