Stimulation of prostaglandin E2-synthesis by noradrenaline in primary cell cultures from rabbit splenic pulpa is mediated by atypical ?-adrenoceptors

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Abstract
In primary cell cultures originating from rabbit splenic pulpa the effects of various adrenoceptor agonists on prostaglandin (PG)-synthesis were studied. The cells-microscopically identified as fibroblasts-released PGs into the medium: especially PGE2 besides small amounts of PGF2α and PGD2. Noradrenaline increased dose-dependently the amount of PGs released into the medium. Besides noradrenaline, only the catecholamines adrenaline and α-methylnoradrenaline strongly activated PG-synthesis. Other α-adrenoceptor agonists like the phenylethylamine and imidazoline derivatives were only weak agonists or completely ineffective. All adrenoceptor agonists without intrinsic activity in these cells antagonized the noradrenaline effect on PG-synthesis, the imidazolines being more potent antagonists than the phenylethylamines. The β-adrenoceptor agonist isoprenaline stimulated PG-synthesis at high concentrations only. The effects of both noradrenaline and isoprenaline were inhibited by low concentrations of phentolamine and phenoxybenzamine, but not by propranolol. The preferential α2-adrenoceptor antagonists yohimbine and rauwolscine were about 50 times more potent in blocking the noradrenaline effect on PG-synthesis than the more α1-specific antagonist corynanthine. However, prazosin, another α1-adrenoceptor antagonist, was about equipotent with yohimbine. It is concluded that noradrenaline elicits PG-synthesis in rabbit splenic fibroblasts via α-adrenoceptor stimulation. The α-adrenoceptor involved has properties which are different from those reported so far for α1- or α1-adrenoceptors.