| Abstract: | Abstract: This study was performed in order to elucidate the mechanism behind the decreased responsiveness to β-adrenergic stimulation occuring in uterine muscle after prolonged treatment with isoprenaline. Pretreatment of rats with isoprenaline, 20 nmol/kg, three times daily during four days, significantly decreased the myometrial relaxing effect of the β-agonist. There was also a significant decrease of the β-receptor binding capacity of the myometrial membranes measured by the (minus;)-(3H) DHA binding technique. In the animals pretreated with isoprenaline no significant increase of the adenylate cyclase activity could be observed after isoprenaline stimulation in vitro. The uterine cAMP level was diminished in the desensitized rats. The phosphodiesterase activity was increased. Thus both decreased production and increased degradation contribute to the lower level of uterine cAMP content. The activity of cAMP dependent protein kinase was also depressed. In this work, where low concentrations of isoprenaline have been administered in vivo, several biochemical parameters have been shown to contribute to the β-adrenergic desensitization in myometrial tissue. |
