Muscarinic M1 receptors stimulate phosphoinositide hydrolysis in bovine cerebral arteries.
The muscarinic agonist oxotremorine-M produced a concentration-dependent increase in phosphoinositide hydrolysis in bovine pial arteries. The maximal effect was 5.9 +/- 0.89 fold over basal levels, and the EC50 for oxotremorine-M was 8.9 x 10(-6) M. The phosphoinositide response in arteries with the luminal endothelium removed was similar to the response in intact arteries. The specific muscarinic antagonists pirenzepine, 4-DAMP and methoctramine produced parallel shifts of the concentration-response curve to oxotremorine-M, with the following order of potency (pKB): 4-DAMP (8.59 +/- 0.10) greater than pirenzepine (8.12 +/- 0.11) greater than methoctramine (6.77 +/- 0.20). These results indicate that muscarinic stimulation activates phosphoinositide hydrolysis in cerebral arteries, and that the muscarinic receptors mediating this increase are similar to the M1 subtype.
Garcia-Villalon
A L
AL
Department of Pharmacology, College of Medicine, University of California, Irvine 92717.
Ehlert
F J
FJ
Krause
D N
DN
Duckles
S P
SP
D000818:Animals; D002417:Cattle; D002536:Cerebral Arteries / Q000187:drug effects / Q000502:physiology*; D003959:Diamines; D004730:Endothelium, Vascular / Q000187:drug effects; D006868:Hydrolysis; D007295:Inositol Phosphates / Q000378:metabolism; D007700:Kinetics; D010095:Oxotremorine / Q000031:analogs & derivatives; D010716:Phosphatidylinositols / Q000378:metabolism*; D010880:Piperidines; D010890:Pirenzepine; D011976:Receptors, Muscarinic / Q000145:classification / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
D003959:Diamines; D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D010880:Piperidines; D011976:Receptors, Muscarinic; D010890:Pirenzepine; D010095:Oxotremorine; C042743:oxotremorine M; C042375:4-diphenylacetoxy-1,1-dimethylpiperidinium; C054938:methoctramine