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Abstract #6495 Published in IGR 3-2
Kappa opioid agonist-induced changes in IOP: correlation with 3H-NE release and cAMP accumulation
Moore TT; Potter DEExperimental Eye Research 2001; 73: 167-178
Opioid receptors have been demonstrated to modulate various functions in the eye. This research project was designed to determine and compare the effects of kappa opioid agonists on selected parameters that influence ocular hydrodynamics. Experiments determined the effects of two relatively selective kappa opioid receptor agonists, ICI 204 448 (ICI), which has limited ability to penetrate the blood-brain barrier, and spiradoline mesylate on: (1) in vivo parameters, intraocular pressure (IOP), and pupil diameter (PD); and (2) in vitro parameters, neurotransmitter release and cAMP accumulation, in the ciliary body. Dark-adapted, reverse light cycle New Zealand white (NZW) male rabbits were used in all the experiments. In in vivo experiments, IOPs and PDs were measured by a pneumatonometer and an optistick, respectively, before and after drug administration. Baseline readings were taken at 0.5 and zero hours prior to agonist administration. Post-drug IOP and PD measurements were made at 0.5, one, two, three, four, and five hours after agonist application. In some experiments, the relative selective kappa antagonist, norbinaltorphimine was applied 30 minutes prior to agonist application. In in vitro experiments, the release of tritiated norepinephrine (3H-NE) was measured from perfused electrically stimulated iris ciliary bodies, and expressed as the percentage change of the control. Basal and isoproterenol-stimulated cAMP concentrations in iris ciliary bodies were quantified by radioimmunoassay techniques in the presence and absence of ICI and spiradoline. ICI and spiradoline decreased IOP in a dose-dependent manner in normal rabbits, but only spiradoline produced significant changes in PD. The kappa opioid receptor antagonist, norbinaltorphimine, antagonized the hypotensive effects of spiradoline and ICI IOP experiments. Both kappa agonists inhibited the release of norepinephrine from perfused iris ciliary bodies. Isoprotenerenol-stimulated cAMP levels in iris ciliary bodies were suppressed by both kappa receptor agonists. The antagonism by norbinaltorphimine suggests that ICI and spiradoline lower IOP by activating kappa opioid receptors in the eye. The bilateral effects of unilaterally applied spiradoline on PD indicate that this kappa agonist activates receptors in the iris and/or brain. The inhibition of norepinephrine release and cAMP accumulation in the iris ciliary body by ICI and spiradoline suggests that there are both pre- and postjunctional sites of action for kappa agonists.
Dr T.T. Moore, Department of Pharmacology and Toxicology, Morehouse School of Medicine, Atlanta, GA, USA
Classification:
11.4 Prostaglandins (Part of: 11 Medical treatment)