IN PRIMARY NEURONAL CULTURES MUSCARINIC M1 AND M3 RECEPTOR MESSENGER-RNA LEVELS ARE REGULATED BY AGONISTS, PARTIAL AGONISTS AND ANTAGONISTS

The homologous regulation of the muscarinic m1 and m3 receptors mRNA w as studied in rat corticostriatal neuronal cultures. In response to th e full agonist carbachol the m1 and m3 receptor mRNA levels were modul ated and showed different time-courses. The m1 receptor mRNA increased to 270% of prestimulation levels after 6 h, while the m3 receptor tra nscript transiently increased to 170% after 2 h. Conversely, the musca rinic receptor partial agonist oxotremorine caused a rapid and sustain ed increase in both mRNA species as soon as after 1 h of exposure. A c omparable increase in both receptor mRNAs was induced by the partial a gonist orophenylcarbamoyloxy)-2-butynyltrimethyl-ammonium chloride] (M cN-A-343). The observation that 1 h exposure to the non selective anta gonist N-methyl-scopolamine also enhanced the mi and m3 receptor trans cripts suggests that in corticostriatal neurons muscarinic receptor pa rtial agonists exert an antagonist-like effect on the m1 and m3 recept or mRNAs.