Actions of indomethacin and prostaglandins E2 and D2 on nerve transmission in the nictitating membrane of the cat.
The effects of PGE2, PGD2 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. PGD2 depressed neurotransmission throughout a broad range of stimulus free quencies, apparently by presynaptic inhibition of norepinephrine release. PGE2 enhanced the effects of both nerve stimulation and exogenous norepinephrine in intact preparations but only depressed the effects of exogenous norepinephrine in the chronically denervated nictitating membrane, suggesting that part of the effect of PGE2 on neurotransmission was presynaptic. When norepinephrine reuptake was blocked by desipramine, PGE2 still enhanced neurotransmission. Indomethacin, but not other cyclooxygenase inhibitors (aspirin, ibuprofen, flurbiprofen, meclofenamic acid), inhibited the response of the nictitating membrane to nerve stimulation without depressing the effects of exogenous norepinephine. Curiously, indomethacin, but again not other cyclooxygenase inhibitors, specifically antagonized the ability of PGE2 to enhance nerve transmission. These results further characterize the pharmacological effects of PGE2 and PGD2 at the nictitating membrane. The lack of effect of cyclooxygenase inhibitors suggests that neither endogenous PGE2 or PGD2 play a functional role at this synapse. The effects of indomethacin appear to be unrelated to inhibition of prostaglandin synthesis.
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D015232:Dinoprostone; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology*; D007269:Injections, Intra-Arterial; D008297:Male; D009541:Nictitating Membrane / Q000187:drug effects / Q000294:innervation*; D011453:Prostaglandins / Q000494:pharmacology*; D011457:Prostaglandins D / Q000494:pharmacology*; D011458:Prostaglandins E / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects*; D013806:Theophylline / Q000494:pharmacology
D011453:Prostaglandins; D011457:Prostaglandins D; D011458:Prostaglandins E; D001285:Atropine; D013806:Theophylline; D015232:Dinoprostone; D007213:Indomethacin