Evidence that a GABAA-like receptor is involved in progesterone-induced acrosomal exocytosis in mouse spermatozoa.
We have investigated whether progesterone-triggered acrosomal exocytosis involves the activation of a gamma-aminobutyric acid (GABA) receptor, and whether activation of this receptor is linked to Ca2+ entry via Ca2+ channels. Mouse spermatozoa preincubated in a modified Tyrode's medium underwent exocytosis when stimulated with progesterone, as revealed by an increase in the number of cells exhibiting an "AR" pattern after staining with chlortetracycline; the effect was concentration dependent. Only capacitated spermatozoa underwent exocytosis in response to progesterone: cells preincubated for 15 min (uncapacitated) did not exocytose in response to this agonist, whereas cells preincubated for 120 min did. Stimulation of capacitated spermatozoa with GABA or muscimol, two GABAA receptor agonists, resulted in acrosomal exocytosis; this response was enhanced by half-maximal concentrations of progesterone. Bicuculline, a GABAA receptor antagonist, inhibited exocytosis stimulated by progesterone or GABA. Picrotoxin, another GABAA receptor antagonist, inhibited only GABA-stimulated exocytosis. These results suggest that progesterone effects are mediated by a GABAA receptor but that such receptor may not be identical to the neuronal GABAA receptor. The ability of progesterone, GABA, or muscimol to stimulate exocytosis was blocked by the Ca2+ channel antagonists verapamil or nifedipine. The Ca2+ channel agonist Bay K 8644, on the other hand, stimulated exocytosis in capacitated sperm cells. The stimulatory ability of progesterone and Bay K 8644 was additive. These results indicate that acrosomal exocytosis involves activation of a GABAA receptor apparently linked to Ca2+ channels.
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Department of Development and Signalling, Babraham Institute, Cambridge, United Kingdom.
Roldan
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D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000177:Acrosome / Q000502:physiology*; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D005089:Exocytosis / Q000187:drug effects*; D008297:Male; D051379:Mice; D009118:Muscimol / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D011374:Progesterone / Q000494:pharmacology*; D011963:Receptors, GABA-A / Q000502:physiology*; D013075:Sperm Capacitation; D013094:Spermatozoa / Q000187:drug effects / Q000648:ultrastructure*; D014700:Verapamil / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D015220:Calcium Channels; D011963:Receptors, GABA-A; D009118:Muscimol; D011374:Progesterone; D005680:gamma-Aminobutyric Acid; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D014700:Verapamil; D009543:Nifedipine; D001640:Bicuculline