THE EFFECTS OF ISOXSUPRINE HYDROCHLORIDE ON THE CYCLIC NUCLEOTIDE SYSTEM IN THE RAT UTERUS

¹ Department of Pharmacology, Mead Johnson Research Center, Evansville, Indiana

The smooth muscle relaxant action of isoxsuprine HCl on rat uterus is apparently mediated via beta adrenergic receptor stimulation because: 1) isoxsuprine stimulated adenylyl cyclase activity in the uterus, 2) the stimulation of adenylyl cyclase was susceptible to blockade with the beta adrenergic receptor blocker, sotalol, 3) the drug produced significant elevations in the intracellular levels of cyclic adenosine monophosphate in the uterus both in vitro and in vivo and 4) the elevations in intracellular cyclic adenosine monophosphate levels preceded the relaxant effects of the drug. Isoxsuprine also lowered the intracellular levels of cyclic guanosine monophosphate in the uterus. This latter action is apparently indirect since the drug did not affect guanylyl cyclase activity. Since the inhibitory potency of isoxsuprine on cyclic nucleotide phosphodiesterase in vitro is rather weak, that action of the drug probably plays only a minimal role in its in vivo effects.