Prejunctional prostaglandin receptors in the human iris-ciliary body.
Prostaglandins (PGs) of the E series have been shown to modulate sympathetic neurotransmitter release in a variety of peripheral tissues and organs, including the eye. In this study, we evaluated the inhibitory effects of a series of naturally-occurring and synthetic PGs on field stimulation-evoked release of 3H-norepinephrine (3H-NE) from isolated, superfused segments of human iris-ciliary body. Field-stimulated 3H-NE secretion was calcium-dependent, blocked by selective inhibitors of voltage-sensitive calcium and sodium channels, and originated from a desipramine-sensitive transmitter pool. Evoked 3H-NE release was inhibited in a concentration-dependent manner by PGE2 (EC50 = 45 nM) and several closely related compounds with the following rank order of potency: sulprostone greater than 16,16-dimethyl-PGE2 greater than PGE2 greater than 11-deoxy-PGE1. By contrast, PGF2 alpha was relatively inactive (EC50 greater than 10 microM) in this system. None of the above compounds significantly modified spontaneous 3H-NE efflux. PGE2-mediated inhibition was not antagonized by the selective prostanoid EP1-receptor antagonists AH 6809 (10 microM) or SC-19220 (30 microM), nor did these agents alone affect basal or field-stimulated 3H-NE release. The results suggest that human ocular sympathetic nerves possess inhibitory PG receptors which have the pharmacological properties of the EP3 subtype. These receptors may play a role in local feedback regulation of sympathetic transmission in the iris-ciliary body, and may contribute to symptoms of acute ocular inflammation, including vasodilation, miosis and hypotony.
Ohia
S E
SE
Department of Ophthalmology and Visual Sciences, University of Louisville School of Medicine, Kentucky Lions Eye Research Institute 40292.
Jumblatt
J E
JE
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015220:Calcium Channels / Q000378:metabolism; D002924:Ciliary Body / Q000294:innervation / Q000378:metabolism*; D004558:Electric Stimulation; D006801:Humans; D007498:Iris / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D008875:Middle Aged; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D011458:Prostaglandins E / Q000494:pharmacology; D011459:Prostaglandins E, Synthetic / Q000494:pharmacology; D011982:Receptors, Prostaglandin / Q000378:metabolism*; D015222:Sodium Channels / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000378:metabolism
D015220:Calcium Channels; D011458:Prostaglandins E; D011459:Prostaglandins E, Synthetic; D011982:Receptors, Prostaglandin; D015222:Sodium Channels; D009638:Norepinephrine