THE PRESENCE OF ANTAGONISTICALLY ACTING ALPHA AND BETA ADRENERGIC RECEPTORS IN THE MOUSE SPLEEN

¹ Laboratory of Chemical Pharmacology, National Heart Institute, National Institutes of Health, Bethesda, Maryland

The data presented in this report indicate that both alpha and beta adrenergic receptors exist in the spleen of the mouse. Responses of the isolated whole spleen were measured by a sensitive isotonic transducer. Contractions elicited by l-norepinephrine (l-NE), l-epinephrine (l-E) and dl-isoproterenol (dl-ISO) were antagonized reversibly by phentolamine and irreversibly by phenoxybenzamine. Low and high concentrations of dl-ISO produced relaxation and contraction, respectively, of splenic smooth muscle. The relaxation elicited by dl-ISO was reversibly antagonized by propranolol and MJ 1999 (4-(2-isopropylamino-1-hydroxyethyl)methanesulfonanilide hydrochloride). In the presence of phenoxybenzamine, an alpha receptor antagonist, only relaxation was elicited by l-E and dl-ISO. Intrinsic activities (alpha) and affinities (pD₂) of _l-NE, _l-E and _dl-ISO for alpha receptors were determined. Activities for alpha receptors fell in the order dl-ISO l-NE l-E. Affinities for alpha receptors increased in the order, dl-ISO _l-E _l-NE. The relative order of increasing intrinsic activities for beta receptors was the reverse of that for alpha receptors, l-NE l-E dl-ISO. The affinities of reversible and irreversible antagonists, pA₂ and pD'₂ values, respectively, for alpha receptors were also determined.