Ca. Taira, MUSCARINIC RECEPTOR SUBTYPE INVOLVEMENT IN BRAIN CHOLINERGIC STIMULATION BY INTRACEREBROVENTRICULAR NEOSTIGMINE IN SINOAORTIC DENERVATED RATS, General pharmacology, 31(4), 1998, pp. 583-588
1. The present studies evaluated the participation of central muscarin
ic receptors in the cardiovascular effects of centrally injected neost
igmine, a quaternary anticholinesterase, in conscious, sham operated r
ats and in sinoaortic denervated animals. 2. The dose dependent presse
r effect of neostigmine (0.1 to 1 mu g ICV) was greater in sinoaortic
denervated rats than in sham operated animals, but only a dose-depende
nt bradycardic effect was seen in sham operated rats. 3. Doses of 3.3
nmol (ICV) of both the Mi muscarinic antagonist, pirenzepine, and the
M-3 muscarinic antagonist, 4-DAMP, prevented the presser response to 1
mu g of neostigmine in sham-operated rats and in sinoaortic denervate
d animals; however, the MZ 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 (ICV) of b
oth pirenzepine and 4 DAMP prevented the bradycardic response to 1 mu
g (ICV) of neostigmine, whereas AF-DX116 induced a partial blockade. 4
. 4-DAMP, at the dose of 0.3 nmol (ICV), but not pirenzepine at the sa
me dose, prevented the presser effect of neostigmine (0.1 co 1 mu g IC
V) in both groups of rats. Both muscarinic antagonists at this dose pr
evented the bradycardia elicited by the anticholinesterase (0.1 to 1 l
ag ICV), but 4-DAMP showed a greater antagonistic action on this cardi
ac effect than pirenzepine. In sham operated rats, ICV injection of 0.
3 nmol of AF-DX116 failed to modify the cardiovascular responses to 0.
3 mu g of neostigmine. 5. Results suggest mainly an involvement of bra
in M-3-subtype muscarinic receptors in the cardio vascular effect of i
ntracerebroventricular administration of anticholinesterase neostigmin
e in both groups of rats. (C) 1998 Elsevier Science Inc.