Adenosine and neuropeptide Y enhance alpha 1-adrenoceptor-induced accumulation of inositol phosphates and attenuate forskolin-induced accumulation of cyclic AMP in rat vas deferens.
The action on alpha 1-adrenoceptor-coupled polyphosphoinositide breakdown of two modulators of adrenergic neurotransmission, adenosine and neuropeptide Y (NPY), was studied in pieces of rat vas deferens. Both adenosine and NPY dose-dependently increased the accumulation of inositol phosphates induced by phenylephrine (50 microM), but neither of the two compounds had any effect alone on inositol phosphate accumulation. In parallel experiments, adenosine and NPY dose-dependently decreased forskolin-induced cyclic AMP accumulation without affecting resting levels. Phenylephrine slightly increased forskolin (1 microM)-induced cyclic AMP accumulation, whereas treatment with agents that increase or mimic cyclic AMP (forskolin, prostaglandin E2, 8-Br-cyclic AMP) had no significant effect on phenylephrine-induced inositol phosphate accumulation. The previously described potentiation of the alpha 1-adrenoceptor-mediated contractile responses of the rodent vas deferens by adenosine and NPY is suggested to result from an enhanced alpha 1-adrenoceptor-induced accumulation of inositol triphosphate. Possible mechanisms are discussed.
Häggblad
J
J
Department of Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Fredholm
B B
BB
D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D007295:Inositol Phosphates / Q000378:metabolism*; D008297:Male; D009478:Neuropeptide Y / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D013268:Stimulation, Chemical; D013403:Sugar Phosphates / Q000378:metabolism*; D014649:Vas Deferens / Q000378:metabolism*
D007295:Inositol Phosphates; D009478:Neuropeptide Y; D011942:Receptors, Adrenergic, alpha; D013403:Sugar Phosphates; D005576:Colforsin; D010656:Phenylephrine; D000242:Cyclic AMP; D000241:Adenosine