THE CHOLINERGIC RECEPTOR-LINKED PHOSPHOINOSITIDE METABOLISM IN MOUSE CEREBRUM AND CEREBELLUM IN-VIVO

The cholinergic receptor-linked poly-phosphoinositide hydrolysis was s tudied in mouse cerebrum and cerebellum after prelabeling the brain wi th [H-3]inositol. I.p. injection of Li (8 meq/kg) to C57Bl/6J mice for 4 h resulted in 14- and five-fold increases in [H-3]inositol-labeled inositol monophosphate (IP1) in cerebrum and cerebellum, respectively. The labeled inositol bisphosphate (IP2) was also increased 83 and 19% in cerebrum and cerebellum, respectively. Prior injection of atropine (100 mg/kg) resulted in inhibition of Li-induced increases in labeled IP1 by 74 and 56% in cerebrum and cerebellum, respectively. Administr ation of pilocarpine (20 mg/kg) to the Li-treated mice for 30 min resu lted in further increases in labeled IP1 and IP2 and a concomitant dec rease in labeled inositol in cerebrum but not in cerebellum. Mass meas urements of IP1 and IP2 isomers by HPLC revealed that inositol 1-monop hosphate (Ins(1)P), inositol 4-monophosphate (Ins(4)P) and inositol 1, 4-bis-phosphate (Ins(1,4)P2) were all increased by pilocarpine adminis tration in the Li-treated mouse cerebrum. The effects of pilocarpine a dministration in mouse cerebrum (increases in IP1 and IP2) could be co mpletely inhibited by preinjection of atropine. Atropine injection als o decreased the levels of inositol 1,4,5-trisphosphate [Ins(1,4,5)P3]. Surprisingly, a decrease in Ins(1,4,5)P3 level was also found in non- Li-treated mice after pilocarpine administration (30 mg/kg, 10-40 min) . Except for the increase (20%) in [P-32]-labeled PIP in the cerebrum, Li or Li together with pilocarpine administration did not alter the l evels of [H-3]inositol or [P-32]phosphate-labeled phosphoinositides. T aken together, these results demonstrated the ability of using choline rgic agonists and antagonists to probe the cholinergic receptor-linked poly-phosphoinositide signaling activity in brain and that these resp onses are more active in the cerebrum as compared with the cerebellum.