M3-muscarinic receptor mediates prejunctional inhibition of noradrenaline release and the relaxation in cat femoral artery.
The aim of the present study was to analyse the muscarinic receptors involved in the vasodilation elicited by acetylcholine (ACh) and the carbachol inhibition of electrically-evoked [3H]noradrenaline (NA) release in cat femoral artery. For this purpose, the following receptor antagonists were used, atropine, pirenzepine (M1-antagonist), AF-DX 116 (M2-antagonist) and 4-diphenylacetoxy-N-methylpiperidine methobromide (4-DAMP; M3-antagonist). The order of potency (pA2 values) of these drugs at postjunctional level was: atropine (9.7) greater than or equal to 4-DAMP (9.6) greater than pirenzepine (7.2) greater than AF-DX 116 (6.0), and at prejunctional level (pIC50 values) was: 4-DAMP (9.3) greater than atropine (8.5) greater than AF-DX 116 (7.1) greater than pirenzepine (5.9). These findings indicate that the muscarinic receptors mediating the vasodilation induced by ACh and the carbachol inhibition of NA release are of the M3-subtype.
Departamento de Farmacologia y Terapéutica, Facultad de Medicina, Universidad Autónoma, Madrid, Spain.
F A
FA
Fernándes
M J
MJ
Alonso
J
J
Marín
M
M
Salaices
D000109:Acetylcholine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D002217:Carbachol / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002415:Cats; D004558:Electric Stimulation; D004730:Endothelium, Vascular / Q000187:drug effects*; D005260:Female; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009451:Neuroeffector Junction / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism*; D010276:Parasympatholytics / Q000494:pharmacology*; D011976:Receptors, Muscarinic / Q000187:drug effects*
D010276:Parasympatholytics; D011976:Receptors, Muscarinic; D002217:Carbachol; D000109:Acetylcholine; D009638:Norepinephrine