Antagonist discrimination of two muscarinic responses elicited by applied agonists and orthodromic stimuli in superior cervical ganglion of rabbit.

Abstract:

:Pirenzepine and gallamine selectively and differentially antagonized two muscarinic responses, in the superior cervical ganglion of the rabbit, whether elicited by the muscarinic agonist methacholine or by orthodromic stimulation. Methacholine elicited a biphasic ganglionic response, consisting of hyperpolarizing and depolarizing components that were the agonist-induced equivalents of the slow-inhibitory and slow-excitatory postsynaptic potentials elicited by orthodromic stimulation. Superfusion of ganglia with pirenzepine resulted in a concentration-dependent suppression of depolarization induced by methacholine with no suppressant action on ganglionic hyperpolarization. In contrast, superfusion of ganglia with gallamine resulted in a concentration-dependent suppression of ganglionic hyperpolarization and the slow-inhibitory postsynaptic potential. These effects occurred without appreciable suppression of ganglionic depolarization or the slow-excitatory postsynaptic potential. The action of gallamine was specific for muscarinic hyperpolarization. Hyperpolarizations produced by superfusion with dopamine or norepinephrine were unaffected by gallamine, at concentrations that suppressed the muscarinic slow-inhibitory post-synaptic potential. Incubation with anti-cholinesterases produced a parallel shift, to the right, of concentration-response curves for suppression by gallamine of the slow-inhibitory postsynaptic potential. This was presumably the consequence of an increase in the acetylcholine available for interaction with the muscarinic receptor. The evidence suggests that the ability of gallamine and pirenzepine to suppress selectively the slow-inhibitory and slow-excitatory postsynaptic potentials, as previously demonstrated, is through an action at muscarinic receptors. Furthermore, the data suggest that these pharmacological agents produce their effects by interaction at different muscarinic recognition sites.

journal_name

Neuropharmacology

journal_title

Neuropharmacology

authors

Yarosh CA,Ashe JH

doi

10.1016/0028-3908(87)90001-3

subject

Has Abstract

pub_date

1987-11-01 00:00:00

pages

1549-60

issue

11

eissn

0028-3908

issn

1873-7064

journal_volume

26

pub_type

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