Degree Name

Master of Science (MS)

Semester of Degree Completion

1986

Thesis Director

Kip L. McGilliard

Abstract

Caffeine, theophylline, and a number of other xanthine analogues have been shown to stimulate the motility of mammalian spermatozoa. The mechanism by which these compounds act was assumed to be cAMP phosphodiesterase inhibition. However, it has recently been shown that many of the responses elicited by alkylxanthines and their analogues in various tissues are not the result of cAMP phosphodiesterase inhibition but by antagonism of endogenous adenosine. Using the recently described transmembrane migration method this study observed the effect of a number of xanthine and adenosine analogues on mammalian sperm motility. The hypothesis to be tested was that the increase in the motility of mammalian sperm is the result of antagonism of adenosine, at the A1 receptor, by alkylxanthines. Caffeine, theophylline, 1-methylxanthine, 3-methylxanthine and 3-propylxanthine (enprofylline) all increased sperm motility significantly above control. Adenosine also produced a small, but significant, stimulation of motility. N6-cyclohexyladenosine (CHA), a potent A1 adenosine receptor agonist, decreased motility from 10-11M to 10-6M but motility returned to normal as the concentration of CHA was increased from 10-6M to 10-3M. Maximum inhibition of motility was produced at 10-6M CHA. Theophylline is a known adenosine receptor antagonist, while enprofylline is believed to lack significant adenosine antagonistic properties. Both theophylline and enprofylline reversed the inhibitory effects of 10-6M CHA. It was, therefore, concluded that the alkylxanthine stimulation of mammalian sperm motility is the result of a mechanism other than adenosine antagonism.

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