Effects of beta-adrenergic agonists on rat uterine motility and cAMP level in vivo.
Intravenous injection of isoprenaline and salbutamol into rats caused an inhibition of the spontaneous contractions of uterus and increased the uterine cAMP level in a dose-dependent manner. The effects of isoprenaline (0.036 nmol/kg) were diminished or completely prevented by propranolol (0.07-7 mumol/kg). Intravenous infusion of the beta-adrenergic agonists during one hour increased the uterine cAMP level. The highest level of cAMP measured was at 3 min. after start of infusion, thereafter it declined first rather fast but later more slowly. This time pattern of cAMP was very similar to what was seen during incubation of uterine tissue with isoprenaline in vitro. Pretreatment with isoprenaline three times daily 4-7 days before the experiments, decreased both the degree of inhibition and the increase of cAMP in uterus caused by an intravenous injection of isoprenaline. A slight effect on the cAMP rise was detectable after one day of pretreatment, and it seemed to have reached its maximal effect after 4 days, since no further decline in the cAMP response was seen when the pretreatment was prolonged. A dessensibilization to beta-adrenergic agonists was thus seen in uterus after excessive stimulation of isoprenaline in vivo.
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007545:Isoproterenol / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D013997:Time Factors; D014590:Uterine Contraction / Q000187:drug effects*; D014599:Uterus / Q000378:metabolism*
D000318:Adrenergic beta-Agonists; D011433:Propranolol; D000242:Cyclic AMP; D007545:Isoproterenol; D000420:Albuterol