Inhibitory effect of prostaglandins on dopamine release from the retina.
1. Prostaglandins have been shown to modulate transmitter release from both central and peripheral neuroeffector junctions. In the present study, we examined the effect of prostaglandins on [3H]-dopamine release from isolated, superfused rabbit retina. 2. Both naturally occurring and synthetic prostaglandins produced concentration-dependent reduction of electrically evoked [3H]-dopamine overflow without affecting basal tracer efflux. The rank order of potencies of the agonists was: sulprostone > 16,16-dimethyl PGE2 > PGE2 >> 11-deoxy-PGE1 > PGF2 alpha. 3. The PGE2-mediated inhibition of field stimulated [3H]-dopamine release was not blocked by the selective EP1-receptor antagonist, AH6809 (5-30 microM). 4. The cyclooxygenase inhibitor, flurbiprofen (3 microM) had no effect on basal or evoked [3H]-dopamine overflow nor did it affect the inhibition caused by PGE2 suggesting that endogenous prostaglandins are not involved in the regulation of dopamine release in the retina. 5. The inhibition of [3H]-dopamine release produced by submaximal concentrations of PGE2, apomorphine and melatonin were not additive indicating that presynaptic PGE2, D2- and melatonin receptors coexist at sites for neurotransmitter release and may share a common mechanism for regulation of dopamine release. 6. We conclude that prostaglandin-induced inhibition of electrically evoked [3H]-dopamine release from the rabbit retina may be mediated by specific prostaglandin receptors of the EP3 subtype.
Department of Pharmaceutical Sciences, School of Pharmacy and Allied Health Professions, Creighton University, Omaha, NE 68178.
K H
KH
al-Zadjali
M P
MP
Imler
S E
SE
Ohia
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D004558:Electric Stimulation; D005480:Flurbiprofen / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008550:Melatonin / Q000494:pharmacology; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D011453:Prostaglandins / Q000494:pharmacology*; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000187:drug effects; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D044094:Receptors, Melatonin; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism; D012160:Retina / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D014966:Xanthenes / Q000494:pharmacology; D044004:Xanthones
D016861:Cyclooxygenase Inhibitors; D011448:Prostaglandin Antagonists; D011453:Prostaglandins; D011956:Receptors, Cell Surface; D017448:Receptors, Dopamine D2; D044094:Receptors, Melatonin; D011982:Receptors, Prostaglandin; D014966:Xanthenes; D044004:Xanthones; C053876:6-isopropoxy-9-oxoxanthene-2-carboxylic acid; D005480:Flurbiprofen; D008550:Melatonin; D015232:Dinoprostone; D001058:Apomorphine; D004298:Dopamine