Adenosine 3′, 5′-cyclic monophosphate (cyclic AMP), discovered by Sutherland et al. in 1958, is now considered to be the secondary messenger of various β-adrenergic actions, such as cardiac inotropic action, glycogenolysis, lipolysis and relaxation of several smooth muscles. (1) Many investigators have already detected the presence of inhibitory β-adrenergic receptors in the vas deferens of some mammals. (2) Phosphodiesterase inhibitors (i. e. aminophylline, theophylline and papaverine) can reduce or abolish contractions of the vas deferens or rabbits, guineapigs and rats. (3) Externally applied dibutyryl cyclic AMP, a derivative of cyclic AMP, can reduce or abolish contractions of the vas deferens of guinea-pigs, rats and humans.
From the above-mentioned previous reports by many authors, it may be suggested that cyclic AMP is the intracellular mediator of inhibitory β-adrenergic action of the vas deferens smooth muscle.
In this paper, changes in tissue cyclic AMP levels of the rat vas deferens following administration of catecholamines, adrenergic blocking agents and aminophylline have been observed.
The methods were as follows:
1) 9 weeks old male Wistar rats (216±21g), anesthetized with sodium pentobarbital 50mg/kg i. p., underwent lapalotomy.
2) A drug or drugs were injected into the vena cava inferior.
3) 3, 8, 15, 30 or 60 minutes after the injection, the total length of both vas deferens was excised.
4) Immediately cyclic AMP levels of each tissue were estimated, using the cyclic AMP Assay Kit (Radiochemical Centre, Amersham, England).
The saline-injected group and drug-administered group were compared statistically.
The results obtained were as follows:
1) 20μg/kg of epinephrine or isoproterenol could elevate tissue cyclic AMP levels maximamly 8 minutes after the injection of these drugs.
2) The elevation of tissue cyclic AMP levels induced by the injection of epinephrine or isoproterenol was dose-dependent.
3) Preinjection of propranolol 1.0mg/kg abolished the elevation of tissue cyclic AMP levels induced by the injection of epinephrine 20μg/kg or isoproterenol 20μg/kg. But, preinjection of phenoxybenzamine 1.0mg/kg caused no effects.
4) Aminophylline 50mg/kg neither changed the basal tissue cyclic AMP level nor acted synergistically when combined with epinephrine or isoproterenol.
5) Propranolol 1.0mg/kg, phenoxybenzamine 1.0mg/kg or norepinephrine 0.2-200μg/kg did not change the basal tissue cyclic AMP level.
My results may add some proof to the hypothesis that cyclic AMP is the intracellular mediator of inhibitory β-adrenergic action of vas deferens smooth muscle.
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