Bagetta, G. and Constanti, A. (1991) Muscarinic inhibition of excitatory neurotransmission in guinea-pig olfactory cortex slices: weak antagonism by M3-muscarinic receptor antagonists. European Journal of Pharmacology, 198 (1). pp. 69-75. 10.1016/0014-2999(91)90563-6.
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Dose-dependent depression of the electrically evoked surface-negative field potential (N-wave) produced by bath-superfusion of carbachol was measured in guinea-pig olfactory cortex slices maintained in vitro. The possible involvement of M3 (smooth muscle/glandular) type muscarinic receptors in partly mediating this response was investigated by testing the effectiveness of the muscarinic M3 receptor antagonists hexahydro-sila-difenidol (HHSiD) and p-fluoro-hexahydro-sila-difenidol (p-F-HHSiD). Low doses of HHSiD (10-100 nM) or p-F-HHSiD (up to 1 microM), pre-applied for 30 min, produced no obvious antagonism of carbachol responses. However, a clear competitive-type inhibition of carbachol effects was observed in 250 nM-1 microM HHSiD or 10-50 microM p-F-HHSiD respectively. Schild plot analysis (regression slope constrained to unity) of pooled data yielded pA2 values of 6.6 for HHSiD (n = 6 slices) and 5.5 for p-F-HHSiD (n = 6 slices) respectively, suggesting a weak competitive antagonism by both compounds. In addition, combination experiments using either HHSiD or p-F-HHSiD with atropine, produced dose-ratio shifts close to those predicted for two antagonists competing for a common receptor site. By comparison, another suggested M3-receptor antagonist, 4-diphenyl-acetoxy-N-methyl-piperidine methiodide (4-DAMP) was a potent competitive blocker of carbachol responses. Schild analysis for 4-DAMP versus carbachol gave a pA2 of 7.9 (n = 6 slices). It is concluded that the muscarinic receptors involved in the suppression of the olfactory cortical N-wave possess a low affinity for HHSiD and particularly for p-F-HHSiD, but not 4-DAMP.(ABSTRACT TRUNCATED AT 250 WORDS)
|Departments, units and centres:||Department of Pharmacology > Department of Pharmacology|
|Journal or Publication Title:||European Journal of Pharmacology|
|Deposited By:||Library Staff|
|Deposited On:||25 Nov 2011 09:57|
|Last Modified:||25 Nov 2011 09:57|
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