Carbachol stimulates inositol phosphate formation in rat thalamus slices through muscarinic M3-receptor activation.
In cross-chopped slices from rat thalamus and in the presence of 10 mM LiC1, the cholinergic agonist carbachol stimulated the accumulation of total [3H]inositol phosphates ([3H]IP2 = [3H]IP1 + [3H]IP2 + [3H]IP3). Best-fit values for the concentration-response curve for carbachol after 60 min incubation yielded an EC50 of 44 +/- 6 microM, maximum effect of 199 +/- 6% of basal accumulation and Hill coefficient (nH) of 1.1 +/- 0.1. Carbachol-induced [3H]IPs accumulation was inhibited by 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP; pKi 9.1) and the p-fluoro analogue of hexahydro-sila-difenidol (pF-HHSiD; pKi 8.1). Concentration-response curves for carbachol were shifted to the right in a parallel fashion by pirenzepine (100, 300 and 100 nM). A Schild plot of the data was linear (slope 0.95 +/- 0.04) and yielded a log KD for pirenzepine of -6.8 +/- 0.1. Taken together, these results suggest that carbachol-induced inositol phosphate accumulation in rat thalamus is mediated by muscarinic M3-receptors.
de la Vega
M T
MT
Departmento de Fisiología, Biofisica y Neurociencias, Centro de Investigación y de Estudios Avanzados, México, D.F, México.
Nunez
A
A
Montano
J A
JA
D000818:Animals; D001667:Binding, Competitive / Q000502:physiology; D002217:Carbachol / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007295:Inositol Phosphates / Q000096:biosynthesis / Q000378:metabolism*; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology*; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009924:Organ Culture Techniques; D010880:Piperidines / Q000494:pharmacology; D010890:Pirenzepine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000378:metabolism*; D013788:Thalamus / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D014316:Tritium
D007295:Inositol Phosphates; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D010880:Piperidines; D011976:Receptors, Muscarinic; D014316:Tritium; D010890:Pirenzepine; C042375:4-diphenylacetoxy-1,1-dimethylpiperidinium; D002217:Carbachol; C046773:hexahydrosiladifenidol