EVIDENCE FOR M1 MUSCARINIC CHOLINOCEPTORS MEDIATING FACILITATION OF NORADRENALINE RELEASE IN GUINEA-PIG CAROTID-ARTERY

The muscarinic agonists acetylcholine (1-50 mumol/1), carbachol (1-10 mumol/1) and McN-A-343 (1-50 mumol/l, selective for M1 receptors) increased, in a concentration-dependent manner, the electrically-evoked tritium overflow from guinea-pig carotid arteries preincubated with [H-3]-noradrenaline. The increase caused by acetylcholine was not modified by hexamethonium (300 mumol/l) but was reduced by the muscarinic receptor antagonists methylatropinium (0.5 and 1 nmol/l, non-selective), pirenzepine (1 and 5 nmol/l, M1-selective), methoctramine (1 and 5 mumol/l, M2-selective) and p-fluoro-hexahydro-sila-difenidol (0.1-1 mumol/l, M3-selective). The order of potencies (expressed as negative logarithms of concentrations that reduced by 50% the facilitatory effect of acetylcholine) was: methylatropinium (9.93) > pirenzepine (8.83) > p-fluoro-hexahydro-siladifenidol (6.8 1) greater-than-or-equal-to methoctramine (6.20). These results demonstrate the existence of facilitatory M1 receptors modulating noradrenaline release in blood vessels.