Accumulation of Adenosine 3′,5′-Monophosphate and Relaxation in the Rat Uterus In Vitro

Abstract

Theophylline, diazoxide, and papaverine in low concentrations relaxed the uterus with minimal or no elevation of cyclic AMP (cAMP) levels. In higher concentrations, theophylline relaxed the uterus and increased its cAMP levels, but imidazole reversed the increase in cAMP without causing recontraction. Imidazole and NaF caused uterine contractures but did not detectably decrease cAMP levels until several minutes after the onset of contractures. The uterine relaxations produced by theophylline and/or dibutyryl cAMP in amounts which increased uterine cAMP were not reversed by propranolol. These results eliminate the possibility that propranolol interfered with a relaxant action of cAMP. Along with previous data, these results also show that uterine contractile activity was not determined primarily by the general levels of cAMP and that phosphodiesterase activity in the uterus was insufficient to rapidly affect these cAMP levels. Also, substances like theophylline, diazoxide, and papaverine, postulated to inhibit phosphodiesterase activity, did not bring about their relaxant effects by this mechanism.

Actions of Papaverine, Aspaminol and Bile Salts and Intracellular Cyclic AMP Level

“…It has been reported that papaverine, a potent inhibitor of PDE (2), elevates the intra cellular content of cyclic AMP in rat uterus (5,6). In our previous papers (8,12), we have shown that papaverine strongly inhibited PDE from the rat uterus and increased the in tracellular level of cyclic AMP, while Aspaminol, a synthetic antispasmodic, influenced neither the PDE activity nor the intracellular level of cyclic AMP.…”

“…Further, some workers (3,4,5,6,7,8) have reported that papaverine and isoprenaline increased the intracellular level of cyclic AMP in the intestinal and uterine smooth muscle.…”

Comparison of Actions of Papaverine, Aspaminol and Isoprenaline on Isolated Rat Uterus

“…Recently evidence is presented that papaverine, a smooth muscle relaxant, is a potent inhibitor of phosphodiesterase in rabbit aorta, rat uterus and guinea pig ileum (2,3). More recently certain workers (4,5,6,7,8) have reported that papaverine and isoprenaline increased the intracellular level of cyclic AMP in the intestinal and uterine smooth muscle. These results indicate the possibility that the actions of beta adrenergic stimulants and papaverine are mediated through an increase of the intracellular level of cyclic AMP.…”

Anti-Oxytocin Actions of Papaverine, Aspaminol and Isoprenaline on the Rat Uterus and Intracellular Cyclic Adenosine 3, 5-Monophosphate Level

“…Evidence has recently been presented that papaverine, a smooth muscle relaxant, is a potent inhibitor of phosphodiesterase in the smooth muscle (2, 3). More recently, sonic workers (4, 5,6,7,8) In this paper, a change of the intracellular level of cyclic AMP after exposure of the isolated rat uterus to a test drug is estimated and examined as to whether or not the non competitive anti-oxytocin actions of antispasmodics, papaverine and Aspaminol, and isoprenaline are concerned with the cyclic AMP level in the rat uterus.Virgin female Wistar rats weighing 150 to 200 g were ovariectomized and allowed to recover more than 5 days before beginning an experiment. After sacrificing the ovari ectomized rat by a blow on the neck, the uterine horns were removed and suspended in two similar organ baths of 10 ml.…”

“…Evidence has recently been presented that papaverine, a smooth muscle relaxant, is a potent inhibitor of phosphodiesterase in the smooth muscle (2, 3). More recently, sonic workers (4, 5,6,7,8) In this paper, a change of the intracellular level of cyclic AMP after exposure of the isolated rat uterus to a test drug is estimated and examined as to whether or not the non competitive anti-oxytocin actions of antispasmodics, papaverine and Aspaminol, and isoprenaline are concerned with the cyclic AMP level in the rat uterus.…”