Pressor response to posterior hypothalamic administration of carbachol is mediated by muscarinic M 3 receptor

Abstract

Unilateral microinjection of the acetylcholine receptor agonist carbachol into the posterior hypothalamic nucleus evokes a pressor response in the conscious, freely moving rat. To further localize this response 3.3 or 5.5 nmol of carbachol was microinjected in a volume of 50 nl directly into and outside the region of the posterior hypothalamic nucleus. Administration of carbachol outside the posterior hypothalamic nucleus failed to evoke a change in blood pressure indicating that the carbachol-induced pressor response is mediated from the posterior hypothalamic nucleus. Since posterior hypothalamic administration of atropine completely blocks the carbachol-induced increase in blood pressure and atropine blocks the three pharmacologically identified muscarinic receptor subtypes, methylatropine and progressively more selective muscarinic antagonists were administered into the posterior hypothalamic nucleus prior to 5.5 nmol of carbachol. Microinjection of the M 1/M 2/M 3 muscarinic antagonist methylatropine (0.19–12.5 nmol), the M 1/M 3 antagonist 4-DAMP (4-diphenylacetoxy-N-Methylpiperidine; 0.9–3.6 nmol), the M 1 antagonist pirenzpine (9.5–38 nmol), the M 2 antagonist methoctramine (5.5–44 nmol), or the M 3 antagonist p-F-HHSiD (para-fluoro-hexahydro-sila-difenidol; 2.1–8.3 nmol) inhibited the peak increase in mean arterial pressure and the area under the curve of the change in mean arterial pressure versus time plot in a dose-dependent manner. Log ID 50s calculated for the antagonists from the dose-response curves were found to correlate significantly with the log K is of the antagonists for the muscarinic M 3 receptor subtype. These results demonstrate that the increase in mean arterial pressure evoked by microinjection of carbachol into the posterior hypothalamic nucleus is mediated by the muscarinic M 3 receptor.