Regulation of bovine sperm motility and cyclic adenosine 3',5'-monophosphate by adenosine and its analogues.

Cyclic adenosine 3',5'-monophosphate (cAMP) is known to mediate mammalian sperm function. Progress in understanding the mechanism of the control of cAMP levels in mammalian sperm has been hampered, however, by an inability to identify a physiological regulator of adenylate cyclase. In this report we provide evidence that adenosine, 2'-deoxyadenosine, and a number of other adenosine analogues that activate adenylate cyclase in other tissues stimulate bovine caudal sperm motility, and we suggest that they do so through elevation of cAMP levels. We have demonstrated that these compounds elevate cAMP levels in and stimulate the motility of mature bovine caudal sperm in the same concentration range (20-300 microM). In addition, we report that these same nucleosides, under appropriate conditions, elevate cAMP levels and initiate motility in immature caput sperm. Adenosine analogue structure-activity relationships carried out with caudal sperm indicate that substitution at position 2 in the purine ring in the adenosine molecule leads to enhanced activity, while substitution at the N-6 amino group reduces potency. Nucleosides that do not stimulate motility in caudal sperm do not elevate cAMP levels. We postulate that adenosine is a physiological regulator of sperm motility and suggest that it and its analogues owe their action to elevation of cAMP levels.