Prejunctional inhibitory effects of prostanoids on sympathetic neurotransmission in the rabbit iris-ciliary body.
Both naturally occurring and synthetic prostaglandins (PGs) caused concentration-dependent inhibition of electrically evoked [3H]norepinephrine (NE) overflow from the isolated, superfused rabbit iris-ciliary body without affecting basal tritium efflux. The rank order of potencies of the agonists was: sulprostone greater than 16, 16-dimethyl-PGE2 greater than PGE2 greater than 11-deoxy-PGE1 greater than iloprost (stable PGl2 analog) greater than PGF2 alpha greater than or equal to PGD2. However, the Tx-mimetic, U-46619, was without effect on transmitter release at concentrations up to 1 microM. The selective EP1-receptor antagonists, AH 6809 (30 microM) or SC-19220 (10 microM) had no effect on basal or field-stimulated [3H]NE secretion, nor did they antagonize the PGE2-mediated reduction of evoked [3H]NE overflow. Indomethacin (3 microM) and the 5-lipoxygenase inhibitor, BW A4C (1 microM) were without effect on basal or evoked [3H]NE release, suggesting that endogenously formed arachidonic acid metabolites have no significant modulatory role in this in vitro system. Inhibitory effects of submaximal or maximal concentrations of PGE2 combined with corresponding concentrations of clonidine or carbachol were not additive, suggesting that prejunctional PGE2 receptors coexist with alpha-2 adrenergic and muscarinic receptors at neurotransmitter release sites. In the presence of yohimbine (100 nM) and/or atropine (100 nM), however, the inhibition produced by PGE2 was enhanced markedly, suggesting that tonic activation of prejunctional alpha-2 adrenergic or muscarinic receptors by endogenously released transmitters may impair the response to exogenous PGE2.(ABSTRACT TRUNCATED AT 250 WORDS)
Ohia
S E
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Department of Ophthalmology and Visual Sciences, University of Louisville School of Medicine, Kentucky Lions Eye Research Institute.
Jumblatt
J E
JE
D000818:Animals; D044482:Benzeneacetamides; D002924:Ciliary Body / Q000294:innervation*; D005260:Female; D006877:Hydroxamic Acids / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007498:Iris / Q000294:innervation*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D011453:Prostaglandins / Q000494:pharmacology*; D011817:Rabbits; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D011976:Receptors, Muscarinic / Q000187:drug effects; D011982:Receptors, Prostaglandin / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects*
D044482:Benzeneacetamides; D006877:Hydroxamic Acids; D011453:Prostaglandins; D011942:Receptors, Adrenergic, alpha; D011976:Receptors, Muscarinic; D011982:Receptors, Prostaglandin; C056614:N-(3-phenoxycinnamyl)acetohydroxamic acid; D009638:Norepinephrine; D007213:Indomethacin