gamma-aminobutyric acid (GABA) A and B receptors mediate the stimulatory effects of GABA on the human sperm acrosome reaction: interaction with progesterone

Objective: To evaluate which gamma-aminobutyric acid (GABA) receptor mediat es the stimulatory effects of this neurotransmitter on the human sperm acro some reaction, and to examine the interaction of progesterone, a physiologi c inducer of the acrosome reaction, with the. GABA(A) receptor. Design: Prospective study. Setting: A university clinic of andrology. Patient(s): Men with normal sperm analysis parameters. Intervention(s): None. Main Outcome Measure(s): The acrosome reaction of motile spermatozoa. Result(s): The acrosome reaction was stimulated by GABA in a dose-dependent manner. This effect was inhibited completely by bicuculline, a GABA(A) rec eptor antagonist, and only partially by saclofen, a GABA(B) receptor antago nist. Accordingly, muscimol, a GABA(A) receptor agonist, stimulated the acr osome reaction to the same extent as GABA, whereas baclofen, a GABA(B) rece ptor agonist, was less effective. Preincubation with progesterone followed by the addition of GABA resulted in a significant increase in the percentag e of acrosome-reacted spermatozoa compared with progesterone alone. However , this increase was less than a simple addition of effects, suggesting that GABA and progesterone act through the same receptor and/or use the same me chanism of action. To test this hypothesis, the ability of progesterone to induce acrosome reaction was tested in the presence of bicuculline, which s uppressed the stimulatory effects of progesterone. Given that the GABA(A) r eceptor is linked to the chloride channel, we tested whether picrotoxin, a blocker of this channel, could modulate the effects of progesterone or GABA . Picrotoxin completely suppressed the acrosome reaction induced by progest erone and only partially suppressed that caused by GABA. Conclusion(s): gamma-Aminobutyric acid stimulated the acrosome reaction in human spermatozoa, acting mainly through the GABA(A) receptor and to a less er extent through the GABA(B) receptor. Progesterone interacted with the GA BA(A) receptor to induce the acrosome reaction, and the functional integrit y of the chloride channel was vital for this effect. (C) 1999 by American S ociety for Reproductive Medicine.