Pharmacological characterization of the muscarinic receptors mediating contraction of canine saphenous vein.
1. The muscarinic receptor subtype mediating contraction of the canine saphenous vein has been characterized using a range of muscarinic agonists and subtype-selective antagonists. 2. Oxotremorine M and (+)-cis-dioxolane behaved as full agonists, while in comparison L-660,863 ((+/-)-3-(3-amino-1,2,4-oxadiazole-5-yl)quinuclidine) acted as a partial agonist. SDZ ENS 163 (thiopilocarpine), pilocarpine and McN-A-343 (0.1 microM-0.3 mM) did not elicit a response. The profile of agonist potencies suggests a low receptor reserve for contraction. 3. The rank order of antagonist apparent affinities was 4-DAMP (4-diphenylacetoxy-N-methylpiperidine methiodide; 8.41) > pirenzepine (8.10) > himbacine (7.34) > or = p-F-HHSiD (para-fluoro-hexahydrosiladifenidol; 7.15) > methoctramine (6.23). This antagonist apparent affinity profile is consistent with the activation of muscarinic M1 receptors.
Watson
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Institute of Pharmacology, Syntex Discovery Research, Palo Alto, CA 94304, USA.
Reddy
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H
Eglen
R M
RM
D000818:Animals; D004148:Dioxolanes / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D066298:In Vitro Techniques; D018721:Muscarinic Agonists / Q000494:pharmacology*; D009119:Muscle Contraction; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D010095:Oxotremorine / Q000494:pharmacology*; D010880:Piperidines / Q000378:metabolism; D010890:Pirenzepine / Q000378:metabolism; D043643:Receptor, Muscarinic M1; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000502:physiology; D012501:Saphenous Vein / Q000187:drug effects* / Q000378:metabolism
D004148:Dioxolanes; D018721:Muscarinic Agonists; D010880:Piperidines; D043643:Receptor, Muscarinic M1; D011976:Receptors, Muscarinic; D010890:Pirenzepine; D010095:Oxotremorine; C042375:4-diphenylacetoxy-1,1-dimethylpiperidinium