TY - JOUR T1 - ADENYL CYCLASE IN HUMAN LEUKOCYTES: EVIDENCE FOR ACTIVATION BY SEPARATE <em>BETA</em> ADRENERGIC AND PROSTAGLANDIN RECEPTORS JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 1 LP - 7 VL - 178 IS - 1 AU - HENRY R. BOURNE AU - KENNETH L. MELMON Y1 - 1971/07/01 UR - http://jpet.aspetjournals.org/content/178/1/1.abstract N2 - The effects of drugs on adenyl cyclase activity in isolated human leukocytes were examined in two ways: 1) conversion of radioactive adenosine triphosphate to cyclic adenosine monophosphate (AMP) by broken cell preparations; and 2) accumulation of radioactive cyclic AMP within intact leukoytes after preincubation with radioactive adenine. Synthesis of cyclic AMP was increased by prostaglandin-E1(PGE1) and selected catecholamines, but not by glucagon or adrenocorticotropin. Responses to catecholamines were characteristic of a beta adrenergic receptor, both in order of potency or agonists [isoproterenol = epinephrine &gt; norepinephrine &gt; phenylephrine (= 0)] and in being competitively inhibited by beta adrenergic antagonists (propranolol and MJ-1999) but not by alpha antagonists (phentolamine and Dibenamine). The effect of PGE1 was not blocked by propranolol. PGE1 and isoproterenol at maximally effective doses produced no additive effect on cyclic AMP synthesis, suggesting that both drugs stimulate different receptors, but activate the same adenyl cyclase enzyme. The maximum effect of isoproterenol is only about 15% of that produced by PGE1; the possibility that isoproterenol stimulates adenyl cyclase in a fraction of the leukocytes (or specific types of leukocytes) has not been ruled out. © 1971, by The Williams &amp; Wilkins Company ER -