Actions on indomethacin and prostaglandins E 2 and D 2 on nerve transmission in the nictitating membrane of the cat

Abstract

The effects of PGE 2, PGD 2 and cyclooxygenase inhibitors on sympathetic nerve transmission in the nictitating membrane of anesthetized cats were studied to further characterize the actions of these prostaglandins and to define their possible role as neuromodulators. PGD 2 depressed neurotransmission throughout a broad range of stimulus frequencies, apparently by presynaptic inhibition of norepinephrine release. PGE 2 enhanced the effects of both nerve stimulation and exogenous norephinephrine in intact preparations but only depressed the effects of exogenous norepinephrine in the chronically denervated nictitating membrane, suggesting that part of the effect of PGE 2 on neurotransmission was presynaptic. When norepinephrine reuptake was blocked by desipramine, PGE 2 still enhanced neurotransmission. Indomethacin, but not other cyclooxygenase inhibitors (aspirin, ibuprofen, flurbi-profen, meclofenamic acid), inhibited the response of the nictitating membrane to nerve stimulation without depressing the effects of exogenous norepinephrine. Curiously, indmethacin, but again not other cyclooxygenase inhibitors, specifically antagonized the ability of PGE 2 to enhance nerve transmission. These results further characterize the pharmacological effects of PGE 2 and PGD 2 at the nictitating membrane. The lack of effect of cyclooxygenase inhibitors suggests that neither endogenous PGE 2 or PGD 2 play a functional role at this synapse. The effects of indomethacin appear to be unrelated to inhibition of prostaglandin synthesis.