Carbachol-induced inositol phosphate formation in rat striatum is mediated by both M1 and M3 muscarinic receptors.
In vibratome-cut slices from rat striatum and in the presence of 10 mM LiCl, the cholinergic agonist carbachol stimulated the accumulation of total [3H]inositol phosphates (EC50 11+/-1 microM and maximum effect 546+/-36% of basal). The response to 100 microM carbachol (497+/-24% of basal) was inhibited by muscarinic antagonists (1 microM), the rank order of efficacy being 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP; 100% inhibition) approximately pirenzepine (98+/-3%) > p-fluoro analog of hexahydro-sila-difenidol (pFHHSiD; 90+/-3%) >> methoctramine (32+/-7%) approximately tropicamide (30+/-10%). Antagonist inhibition curves best fit to a single-site model for 4-DAMP (pKi 8.9+/-0.2) whereas, for both pirenzepine and pFHHSiD, the best fit was to the two-site model. The pKi values for the high-affinity (8.3+/-0.2) and low-affinity (6.9+/-0.2) components for pirenzepine-mediated inhibition corresponded to those reported for M1 and M3 receptors, respectively. The pKi values for the high-affinity (8.2+/-0.3) and low-affinity (7.0+/-0.2) components for pFHHSiD inhibition were in good agreement with those reported for M3 and M1 receptors, respectively. Altogether these results indicate that carbachol-induced [3H]inositol phosphate formation in rat striatal slices is mediated by both M1 and M3 muscarinic receptors.
de la Vega
M T
MT
Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados, México, D.F., Mexico.
Nuñez
A
A
Arias-Montaño
J A
JA
D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000096:biosynthesis*; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology; D010890:Pirenzepine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D007295:Inositol Phosphates; D018727:Muscarinic Antagonists; D010880:Piperidines; C058297:4-fluorohexahydrosiladifenidol; D010890:Pirenzepine; C042375:4-diphenylacetoxy-1,1-dimethylpiperidinium; D002217:Carbachol