title: Studies of porcine and human sperm suggesting a role for a sperm glycine receptor/Cl- channel in the zona pellucida-initiated acrosome reaction.
abstract: It is known that Cl- is required for the zona pellucida (zona)- and progesterone-initiated mammalian sperm acrosome reaction (AR). Recent evidence indicates the involvement of a unique progesterone receptor resembling a GABAA receptor/Cl- channel in the latter event. In the study reported here, we investigated whether the in vitro porcine sperm AR initiated by heat-solubilized porcine zonae involves a different receptor/Cl- channel than does the progesterone-initiated AR. Capacitated porcine sperm failed to undergo the zona- and progesterone-initiated AR when suspended in a medium deficient in Cl-. We then employed 1) strychnine, an antagonist of neuronal glycine receptor/Cl- channels at nanomolar concentrations and of GABAA receptor/Cl- channels at micromolar concentrations and 2) (+)-bicuculline, an antagonist of neuronal GABAA receptor/Cl- channels that inhibits glycine receptor/Cl- channels only at higher concentrations. We report here that the zona-initiated AR was inhibited by 50 nM strychnine, but the progesterone-initiated AR required 1 microM for inhibition. Moreover, 1 microM (+)-bicuculline inhibited the progesterone-initiated AR, but the zona-initiated AR required 50 microM for inhibition. In addition, glycine initiated the porcine sperm AR, and that event was inhibited by strychnine and (+)-bicuculline with the same order of potency observed for the zona-initiated AR. Finally, glycine initiated the AR in human sperm, and that initiation was inhibited by 50 nM strychnine. This work provides the first evidence suggesting that a glycine receptor/Cl- channel is involved in the zona-initiated mammalian sperm AR.
authors.affiliation: Department of Cell Biology and Human Anatomy, School of Medicine, University of California at Davis 95616, USA.
authors.forename: C S
authors.initials: CS
authors.lastname: Melendrez
authors.forename: S
authors.initials: S
authors.lastname: Meizel
mesh_terms: D000177:Acrosome / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D018118:Chloride Channels / Q000187:drug effects / Q000378:metabolism*; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D005998:Glycine / Q000494:pharmacology; D018684:Glycine Agents / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D011374:Progesterone / Q000494:pharmacology; D018009:Receptors, Glycine / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013075:Sperm Capacitation / Q000187:drug effects / Q000502:physiology; D013081:Sperm Motility / Q000502:physiology; D013094:Spermatozoa / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D013331:Strychnine / Q000494:pharmacology; D013552:Swine; D015044:Zona Pellucida / Q000187:drug effects / Q000378:metabolism*
chemical_list: D018118:Chloride Channels; D018755:GABA Agonists; D018756:GABA Antagonists; D018684:Glycine Agents; D018009:Receptors, Glycine; D011374:Progesterone; D013331:Strychnine; D005998:Glycine; D001640:Bicuculline