Control of anion and fluid secretion by apical P2-purinoceptors in the rat epididymis.

1. Exogenous adenosine triphosphate (ATP) stimulated the short circuit current (SCC) in primary monolayer cultures of rat epididymal cells when added to the apical but not to the basolateral side of the monolayers. Half-maximal stimulation was achieved at 5 x 10(-8) M ATP. 2. The increase in SCC induced by ATP was dependent on the presence of extracellular Cl in the bathing solutions. 3. The effects of other adenosine derivatives, and purine and pyrimidine nucleotides were studied. Their orders of potency in stimulating SCC were: ATP greater than adenosine diphosphate much greater than adenosine monophosphate, adenosine, and ATP greater than inosine triphosphate greater than guanosine triphosphate greater than cytidine triphosphate. These results indicate that ATP interacts with a P2-purinoceptor at the apical membrane of the epididymal cells. 4. The SCC response to ATP was not blocked by 8-phenyltheophylline, a P1-purinoceptor antagonist or by propranolol. Although pretreatment of the cultures with piroxicam abolished the SCC response to bradykinin, it did not affect the response to ATP. This indicates that the SCC response to ATP was not mediated by an increase in the synthesis of prostaglandins. 5. Serosal to mucosal Cl flux (Js-m Cl) and net water flux were measured in the luminally perfused rat epididymis in vivo. ATP (1 microM) added to the luminal perfusion solution caused an increase in Js-m Cl and net water secretion by the epididymal duct. 6. Since spermatozoa contain a high concentration of ATP, it is proposed that ATP released from spermatozoa may affect anion and fluid secretion by the epididymis. The control of secretion via the apical purinoceptors offers a means by which spermatozoa regulate the fluidity of their own environment.