Studies of blocking mechanisms of carbachol-induced polyphosphoinositide turnover in rat cortical synaptosomes by neuroactive drugs.
1. The incorporation of 32Pi into 4 phospholipids of rat cortical synaptosomes was altered in the presence of carbachol (1 mM), viz. a decrease of phosphatidylinositol-4,5-bisphosphate and phosphatidyl-4-phosphate by 34 and 21%, and an increase of phosphatidylinositol and phosphatidic acid by 52 and 96% of basal controls respectively. 2. The IC30 values calculated from the dose-response curves for drugs affecting carbachol-induced 32Pi incorporation into these phospholipids, and [3H]QNB binding to the cortical synaptosomes were similar for the typical antimuscarinic agents (i.e. atropine, pirenzepine and trihexyphenidyl), and tricyclic antidepressants (i.e. amitriptyline, doxepin and imipramine) studied. 3. The IC30 values obtained for drugs affecting carbachol-induced 32Pi incorporation into these phospholipids, and high potassium-induced 45Ca2+-uptake by this preparation were similar for neuroselective calcium channel blockers (i.e. cinnarizine and flunarizine) studied. 4. Our results suggest that the neuroactive drugs studied can either act at, or beyond the receptor level, perhaps on the availability of calcium ion, to block carbachol-induced polyphosphoinositide turnover in rat cortical synaptosomes.
Wei
J W
JW
Institute of Neurosciences, National Yang-Ming Medical College, Taipei, Taiwan, Republic of China.
Lin
S S
SS
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000378:metabolism*; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism; D010276:Parasympatholytics / Q000494:pharmacology; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*
D000929:Antidepressive Agents, Tricyclic; D002121:Calcium Channel Blockers; D008563:Membrane Lipids; D010276:Parasympatholytics; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; D010743:Phospholipids; D011813:Quinuclidinyl Benzilate; D002217:Carbachol; D011188:Potassium; D002118:Calcium