THE RESPONSE OF ISOLATED STRIPS OF CAT SPLEEN TO SYMPATHOMIMETIC DRUGS AND THEIR ANTAGONISTS

¹ Section of Pharmacology, Eaton Laboratories Division, The Norwich Pharmacal Company, Norwich, New York

Epinephrine, norepinephrine and isoproterenol produced concentration-dependent contraction of isolated strips of cat spleen. The order of potency was: epinephrine > norepinephrine > isoproterenol. Receptor protection experiments revealed that the catecholamines produced a contraction through common receptors. The alpha adrenergic blocking drugs tolazoline and Dibenamine antagonized all 3 catecholamines. These data indicated that the splenic receptors for catecholamines were identical and could be classified as alpha adrenotropic receptors.

The beta adrenergic blocking drug DCI specifically antagonized the contractile effects of isoproterenol and, in addition, DCI protected catecholamine receptors from blockade by Dibenamine or phenoxybenzamine thus suggesting that DCI could exert an action, either direct or indirect, on alpha adrenergic receptors.

Low (noncontractile) concentrations of isoproterenol inconsistently produced modest relaxation in strips placed in a state of tone by prior addition of epinephrine, norepinephrine or histamine. This relaxation appeared amenable to blockade by DCI and suggested the presence of inhibitory receptors in spleen. Concentrations of isoproterenol which produced a contraction in resting strips caused relaxation when added to strips contracted above the isoproterenol maximum with either epinephrine or norepinephrine indicating that isoproterenol can be classified as a partial agonist at alpha adrenotropic receptors.