Differential regulation of subtypes m1-m5 of muscarinic receptors in forebrain by chronic atropine administration.
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Wall SJ, Yasuda RP, Li M, Ciesla W, Wolfe BB
Differential regulation of subtypes m1-m5 of muscarinic receptors in forebrain by chronic atropine administration.
J Pharmacol Exp Ther. 1992 Aug;262(2):584-8.
- PubMed ID
- 1323653 [ View in PubMed]
- Abstract
The regulation of individual muscarinic receptor subtypes in rat cerebral cortex/dorsal hippocampus was examined following 14-day administration of the nonselective antagonist atropine. Total muscarinic receptor density increased 24%, from 2196 fmol/mg to 2722 fmol/mg. The nature of this increase was examined using a panel of antisera selective for the m1 to m5 muscarinic receptors. Thus, 97% of all cortical/hippocampal receptors were accounted for by immunoprecipitation. Three subtypes were observed to increase significantly in density: m1 receptor from 824 to 982 fmol/mg (19%, P less than .05); m2 receptor from 476 to 519 fmol/mg (9%, N.S.); m3 receptor from 259 to 438 fmol/mg (69%, P less than .001); m4 receptor from 574 to 638 fmol/mg (11%, P less than .05); and the m5 receptor from 23 to 38 fmol/mg (65%, N.S.). Receptors coupled to the hydrolysis of phosphoinositides (m1, m3, m5) appeared to be preferentially up-regulated (32% over control levels, P less than .001) compared with those coupled to the inhibition of adenylyl cyclase (m2, m4; 10% over control levels, P less than .05). The absolute density of the molecularly defined m1 and m4 receptors, which reportedly possess the highest affinity for pirenzepine (M1), increased 16% (P less than .05), whereas the density of receptors having the lowest affinity for pirenzepine (m2, m3 and m5) increased 31% (P less than .001) with atropine treatment. When the increase in total receptor density was examined with [3H]pirenzepine, the 16% elevation in high-affinity (m1 and m4) sites was not detected.(ABSTRACT TRUNCATED AT 250 WORDS)
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Atropine Muscarinic acetylcholine receptor M1 Protein Humans YesAntagonistDetails Atropine Muscarinic acetylcholine receptor M2 Protein Humans YesAntagonistDetails Atropine Muscarinic acetylcholine receptor M3 Protein Humans YesAntagonistDetails Atropine Muscarinic acetylcholine receptor M4 Protein Humans YesAntagonistDetails Atropine Muscarinic acetylcholine receptor M5 Protein Humans YesAntagonistDetails