Regulation of [3H]D–Aspartate Release From Mammalian Isolated Retinae by Hydrogen Sulfide

Abstract

Abstract: : Evidence from our laboratory shows that hydrogen sulfide (H₂S) can inhibit sympathetic neurotransmission from isolated porcine iris–ciliary bodies (Ohia et al., ARVO Abstract, 2005). Since relatively high concentrations of H₂S in the brain has been associated with some neurological disorders such as Downs Syndrome (Kamoun et al., Am. J. Med. Gen. 116A:310, 2003), we considered the possibility that this gas may alter excitatory amino acid neurotransmission from mammalian retina. Purpose: To study the pharmacological actions of H₂S (using sodium hydrosulfide, NaHS and sodium sulfide, Na₂S as H₂S donors) on potassium (K⁺)–depolarization evoked release of [³H]D–aspartate from bovine and porcine retinae, in vitro. Methods: Isolated bovine and porcine 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 iso–osmotic concentration of K⁺(50 mM) stimuli applied at 80–88 mins (S₁) and 116–124 mins (S₂) after the onset of superfusion. Results: Both NaHS (1 nM –1 µM) and Na₂S (0.1–10 µM) produced a concentration–dependent inhibition of K⁺–evoked [³H]D–aspartate release from bovine and porcine retinae without affection basal tritium efflux. In general, NaHS was more potent than Na₂S in eliciting inhibition of evoked [³H]D–aspartate overflow regardless of species examined. For instance, in bovine retinae, an equimolar concentration of NaHS and Na₂S (100 nM) caused 40% and 15% inhibition of K⁺–induced [³H]D–aspartate release. An inhibitor of cystathionine ß–synthase, propargylglycine (1 mM) blocked the inhibitory response elicited by NaHS (1 nM) on K⁺–evoked [³H]D–aspartate release from porcine retinae. Conclusions: Both NaHS and Na₂S can inhibit the release of K⁺–evoked [³H]D–aspartate release from bovine and porcine retinae, an action that is dependent on the production of H₂S in these tissues. Further studies are needed to elucidate the mechanism of action of this gas on excitatory amino acid neurotransmission from mammalian retinae.

Keywords: excitatory neurotransmitters • retina • pharmacology