EFFECT OF A BICYCLIC HEXAHYDROAPORPHINE ON POTASSIUM EVOKED [3H]D–ASPARTATE RELEASE FROM PORCINE ISOLATED RETINAE

Abstract

Abstract: : In a previous study, we reported that bicyclic hexahydroaporphines (HHAs) can lower intraocular pressure in normotensive rabbits in a dose–dependent fashion (Saha et al. J. Ocul. Pharmacol. Ther. 13: 497, 1997). Furthermore, we evidenced that HHAs can inhibit ischemia–induced [³H]D–aspartate release from isolated bovine retinae (Roche et al., ARVO abs. no. 3266, 2002). Purpose: To study the effect of nor–HHA on potassium (K⁺) depolarization evoked release of [³H]D–aspartate from isolated, superfused porcine retina. Methods: Isolated neural retinae were incubated in oxygenated Krebs solution containing 200nM of [³H]D–aspartate for 60 mins and then prepared for studies of neurotransmitter release using the superfusion method. Release of [³H]D–aspartate was evoked by an iso–osmotic concentration of K⁺(50 mM), with stimuli applied at 80–88 mins (S₁) and 116–124 mins (S₂) after the onset of superfusion. Nor–HHA was added to the buffer solution 12 mins before and during S₂. Results: Exposure of retinae to successive K⁺–depolarizing stimuli caused an overflow of [³H]D–aspartate yielding S₂/S₁ ratios of unity. Nor–HHA (1 nM – 1 µM) caused a concentration–dependent inhibition of K⁺–depolarization without affecting basal tritium efflux. The highest concentration of nor–HHA (1 µM) tested elicited a 70% inhibition of K⁺–depolarization–evoked release of [³H]D–aspartate release. Conclusions: We conclude that nor–HHA produces an inhibitory action on evoked release of [³H]D–aspartate from porcine isolated retina.

Keywords: neuroprotection • retina • neurotransmitters/neurotransmitter systems