The release of atrial natriuretic factor induced by central carbachol injection may be mediated by muscarinic M1 receptors.
We investigated the effect of selective muscarinic antagonists on atrial natriuretic factor (ANF) release induced by intracerebroventricular (i.c.v) injection of carbachol in the rat. The muscarinic antagonists were given by i.c.v. injection 1 min before carbachol, 1 micrograms/rat. 4-Diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP), a rather selective M1 and M3 receptor antagonist, was the most potent inhibitor of carbachol-induced ANF release, its ID50 being 0.18 nmol/rat. Pirenzepine, a selective M1 antagonist, also potently inhibited the effect of carbachol, its ID50 being 2.74 nmol/rat. The M3-selective antagonist, p-fluoro-hexahydro-sila-diphenidol, was much weaker than pirenzepine, with an ID50 of 57.52 nmol/rat. The selective M2 receptor antagonist, methoctramine, on the other hand, was a very weak inhibitor of carbachol-induced ANF release. The rank order of potency as well as the - log ID50 of the antagonists tested were consistent with their pA2 values for muscarinic M1 receptors, suggesting that this receptor subtype may mediate the central effect of cholinergic mechanisms in the control of ANF release.
Massi
M
M
Istituto di Farmacologia, Università di Camerino, Italy.
Sajia
A
A
Polidori
C
C
Perfumi
M
M
Costa
G
G
Melchiorre
C
C
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002217:Carbachol / Q000008:administration & dosage / Q000494:pharmacology*; D003959:Diamines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007276:Injections, Intraventricular; D007279:Injections, Subcutaneous; D008297:Male; D010276:Parasympatholytics / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D010890:Pirenzepine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*
D003959:Diamines; D010276:Parasympatholytics; D010880:Piperidines; D011976:Receptors, Muscarinic; C058297:4-fluorohexahydrosiladifenidol; D010890:Pirenzepine; C042375:4-diphenylacetoxy-1,1-dimethylpiperidinium; D009320:Atrial Natriuretic Factor; D002217:Carbachol; C054938:methoctramine