Interaction of prostaglandins and clonidine in the rat vas deferens.
Stimulation of presynaptic alpha 2-adrenoceptors by clonidine may lead to local synthesis of prostaglandins which contribute to the inhibition of noradrenaline release observed with this drug. The present investigation was undertaken to determine the role of prostaglandins in the effect of clonidine and xylazine on the rat vas deferens. Both drugs inhibited the twitch response to field stimulation in this preparation. Inhibition was reversed by yohimbine. This effect of clonidine (but not xylazine) was reduced by preincubating vasa deferentia in Krebs containing indomethacin for 1h. Clonidine (but not xylazine) stimulated the synthesis of prostaglandin-like activity in pieces of intact vas deferens incubated in Krebs containing arachidonic acid. Such stimulation was prevented by inclusion of yohimbine (but not prazosin) in the incubation medium. Clonidine did not stimulate prostaglandin synthesis in a cell-free preparation of sheep seminal vesicle microsomes incubated with arachidonic acid or inhibit PGE2 catabolism by purified swine lung 15-PGDH. We conclude that clonidine (but not xylazine) stimulates prostaglandin synthesis possibly by activating phospholipase activity and releasing arachidonic acid from membrane phospholipids. This effect on prostaglandin production is secondary to activation of alpha 2-adrenoceptors.
D000818:Animals; D003000:Clonidine / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects*; D011453:Prostaglandins / Q000096:biosynthesis / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012669:Seminal Vesicles / Q000378:metabolism; D012756:Sheep; D013569:Synapses / Q000378:metabolism; D014649:Vas Deferens / Q000187:drug effects; D015016:Yohimbine / Q000494:pharmacology
D011453:Prostaglandins; D015016:Yohimbine; D003000:Clonidine