Neurotransmitter-induced changes in arachidonate incorporation into rat brain phospholipids: pharmacological manipulations of receptors, presynaptic uptake, mao activity and deacylation-reacylation processes.
The incorporation of [(3)H]arachidonic acid ([(3)H]AA) into phospholipids (PL) of rat brain, was studied in cerebral cortex slices in the presence and absence of norepinephrine (NE), serotonin (5-HT) and carbamylcholine (CCH). Both NE and 5-HT produced a concentration-dependent effect of stimulating [(3)H]AA incorporation into phosphatidylinositol (PI) while attenuating incorporation into other PL. Addition of CCH had no apparent effect. The beta-adrenergic agonist, isoproterenol, had an effect similar to that seen with equimolar concentrations of NE, whereas the alpha(1) agonist, phenylephrine, or the alpha(2) agonist, clonidine, did not produce significant changes. However, application of the NE-receptor blockers, propranolol or prazosin, in the presence of NE, did not modify the NE-induced effects. Similarly, the 5-HT-receptor blockers, methysergide or ketanserine, failed to modify the 5-HT-induced effects, indicating that the neurotransmitter-produced changes may not be receptor mediated. Manipulations of the NE or 5-HT reuptake systems by imipramine (IMI) or desipramine (DMI) had a small additive effect on the neurotransmitter-produced changes in [(3)H]AA incorporation, suggesting that a functional presynaptic reuptake system is not required for the NE or 5-HT-produced effects. The possibility that the NE or 5-HT effects involve the oxidative metabolism of the monoamines by MAO was also investigated. The MAO inhibitors tranylcypromine and pargyline had no appreciable effect on the neurotransmitter-induced changes in [(3)H]AA incorporation whereas clorgyline clearly reduced the increase in [(3)H]AA incorporation into PI seen in the presence of NE or 5-HT, but this clorgyline effect may not be related to its activity as MAO inhibitor. The phospholipase A(2) inhibitor mepacrine had no significant effect on the NE-produced increase in [(3)H]AA incorporation into PI, but it antagonized the NE-produced decrease in [(3)H]AA incorporation into PC. Delta-9-Tetrahydrocannabinol, which acts as acyltransferase inhibitor, antagonized the NE-produced increase in [(3)H]AA incorporation into PI without appreciably influencing the NE-produced decrease in [(3)H]AA incorporation into PC. These findings suggest that the neurotransmitter-produced increase in [(3)H]AA incorporation into PI is mediated by stimulation of a specific lyso-PI arachidonyl transferase. The neurotransmitter effects on arachidonate incorporation may have physiological significance in view of the importance of processes of deacylation and reacylation of membrane PL in regulating the function of neuronal membranes.
Barkai
A I
AI
New York Psychiatric Institute and Department of Psychiatry, Columbia University College of Physicians and Surgeons, 722 W 168th Street, New York, NY 10032, USA.
Murthy
L R
LR