Cathine, an amphetamine-related compound, acts on mammalian spermatozoa via β1- and α2A-adrenergic receptors in a capacitation state-dependent manner

Abstract

BACKGROUND: Mammalian spermatozoa have been shown to have β1,2,3- and α2A-adrenergic receptors, the former functioning only in uncapacitated spermatozoa and the latter only in capacitated cells. Cathine, an amphetaminerelated metabolite of a compound found in Catha edulis leaves, accelerates capacitation and inhibits spontaneous acrosome loss by regulating cAMP production. This study tested the hypothesis that adrenergic receptors are involved in these responses. METHODS: Uncapacitated and capacitated mouse sperm suspensions were incubated with cathine ± specific antagonists for α2- and β-adrenergic receptors for 35 min, then assessed using chlortetracycline fluorescence. Reversibility of receptor accessibility was assessed by depleting suspensions of endogenous decapacitation factor (DF) and then adding crude DF with/without cathine and antagonists. Effects on tyrosine phosphorylation and calcium requirements for both ligand binding and biological responses were also evaluated. RESULTS: Cathine's acceleration of capacitation was blocked by a β1-antagonist, whereas an α2-antagonist blocked inhibition of acrosome reactions. Cathine accelerated capacitation in decapacitated cells, a response inhibited by a β1-antagonist; cathine also stimulated tyrosine phosphorylation. Although calcium was not required for binding, it was needed for responses. CONCLUSIONS: Cathine acts at β1-adrenergic receptors in uncapacitated spermatozoa and at α2A-receptors in capacitated cells; biological activity requires calcium but binding does not. Adrenergic receptor-binding sites can be made reversibly accessible/inaccessible by changing the capacitation state of spermatozoa. These results suggest that amphetamine-related compounds might enhance chances of fertilization in vivo. © The Author 2006. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.