title: Muscarinic receptor subtype involvement in brain cholinergic stimulation by intracerebroventricular neostigmine in sinoaortic denervated rats.
abstract: 1. The present studies evaluated the participation of central muscarinic receptors in the cardiovascular effects of centrally injected neostigmine, a quaternary anticholinesterase, in conscious, sham-operated rats and in sinoaortic denervated animals. 2. The dose-dependent pressor effect of neostigmine (0.1 to 1 microg i.c.v.) was greater in sinoaortic denervated rats than in sham-operated animals, but only a dose-dependent bradycardic effect was seen in sham-operated rats. 3. Doses of 3.3 nmol (i.c.v.) of both the M1 muscarinic antagonist, pirenzepine, and the M3 muscarinic antagonist, 4-DAMP, prevented the pressor response to 1 microg of neostigmine in sham-operated rats and in sinoaortic denervated animals; however, the M2 muscarinic antagonist, AF-DX116, partially blocked this response in sham-operated rats while failing to do so in sinoaortic denervated rats. In sham rats, doses of 3.3 nmol (i.c.v.) of both pirenzepine and 4-DAMP prevented the bradycardic response to 1 microg (i.c.v.) of neostigmine, whereas AF-DX116 induced a partial blockade. 4. 4-DAMP, at the dose of 0.3 nmol (i.c.v.), but not pirenzepine at the same dose, prevented the pressor effect of neostigmine (0.1 to 1 microg i.c.v.) in both groups of rats. Both muscarinic antagonists at this dose prevented the bradycardia elicited by the anticholinesterase (0.1 to 1 microg i.c.v.), but 4-DAMP showed a greater antagonistic action on this cardiac effect than pirenzepine. In sham-operated rats, i.c.v. injection of 0.3 nmol of AF-DX116 failed to modify the cardiovascular responses to 0.3 microg of neostigmine. 5. Results suggest mainly an involvement of brain M3-subtype muscarinic receptors in the cardiovascular effect of intracerebroventricular administration of anticholinesterase neostigmine in both groups of rats.
authors.affiliation: Cátedra de Farmacología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina. ctaira@huemul.ffyb.uba.ar
authors.forename: C A
authors.initials: CA
authors.lastname: Taira
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects*; D002552:Cerebral Ventricles / Q000187:drug effects*; D018678:Cholinergic Agents / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009388:Neostigmine / Q000008:administration & dosage / Q000494:pharmacology*; D017764:Parasympathectomy; D010890:Pirenzepine / Q000494:pharmacology; D051381:Rats; D011976:Receptors, Muscarinic / Q000145:classification / Q000187:drug effects* / Q000502:physiology*; D012850:Sinus of Valsalva / Q000187:drug effects
chemical_list: D018678:Cholinergic Agents; D002800:Cholinesterase Inhibitors; D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D009388:Neostigmine; D010890:Pirenzepine