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 was studied in rat corticostriatal neuronal cultures. In response to the full agonist carbachol the m1 and m3 receptor mRNA levels were modulated and showed different time-courses. The m1 receptor mRNA increased to 270% of prestimulation levels after 6 h, while the m3 receptor transcript transiently increased to 170% after 2 h. Conversely, the muscarinic receptor partial agonist oxotremorine caused a rapid and sustained increase in both mRNA species as soon as after 1 h of exposure. A comparable increase in both receptor mRNAs was induced by the partial agonist [4-(m-chlorophenylcarbamoyloxy)-2-butynyltrimethyl-ammonium chloride] (McN-A-343). The observation that 1 h exposure to the non selective antagonist N-methyl-scopolamine also enhanced the mi and m3 receptor transcripts suggests that in corticostriatal neurons muscarinic receptor partial agonists exert an antagonist-like effect on the m1 and m3 receptor mRNAs.