Potentiation of neurotransmitter release coincides with potentiation of phosphatidyl inositol turnover. A possible in vitro model for long term potentiation.
Carbachol (CCh) a cholinergic agonist which hydrolyses phosphatidyl-inositol bisphosphate (PIP2) to produce the breakdown products inositol trisphosphate (IP3) and diacylglycerol (DAG) was tested for its ability to induce [3H]norepinephrine ([3H]NE) release and to accumulate [3H]inositol phosphate ([3H]IP) under normal and membrane depolarizing conditions. Our results suggest two major points: first, muscarinic acetylcholine receptor (mAChR) agonists and depolarizing agents (of which KCl is the most effective) act in concert to induce potentiation of PI turnover and potentiation of neurotransmitter release. The simultaneous presence of both a depolarizing agent and a receptor agonist is obligatory for eliciting potentiatory effect. Facilitation of release by muscarinic agonist and K+, added together, was 2 to 5-fold above additivity and the levels of [3H]IP accumulated were 3-5-fold above additivity by K+ and CCh. Enhancement of release and of [3H]IP formation is reversed by pirenzepine, a muscarinic (MI) specific antagonist, Kdiss = 0.4 and 0.8 microM, respectively. Second, synergy of IP accumulation in correlation with synergy of neurotransmitter release elicited by mAChR activation and membrane depolarization, suggests a possible role for phospholipase C (PLC) in the bifurcating control of neurotransmitter release and for the involvement of PLC and voltage sensitive channels in mediation of long-term potentiation (LTP).
Diamant
S
S
Department of Biological Chemistry, Hebrew University of Jerusalem, Israel.
Schwartz
L
L
Atlas
D
D
D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D009473:Neuronal Plasticity; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*
D018377:Neurotransmitter Agents; D010716:Phosphatidylinositols; D011976:Receptors, Muscarinic; D002217:Carbachol; D009638:Norepinephrine