Effects of clenbuterol treatment on the relaxant response in rat uterus.
Prolonged treatment with the beta(2)-adrenergic agonist clenbuterol (0.25 mg kg(-1) s.c. once daily for 10 days) produced a reduction of the relaxant response and cAMP production mediated by stimulation of beta-adrenoceptors in oestrogen-treated rat uterus. Substantial decreases in the relaxant effect of isoproterenol is observed in uterine rings precontracted with 50 mM KCl from clenbuterol-treated rats. The recovery of the relaxant response was also studied and significant differences were seen between acute and prolonged treatment with clenbuterol (P<0.05 vs control). In contrast the relaxant effect of forskolin and 3-isobutyl-1-methylxanthine was similar in untreated or treated rats. Sodium fluoride also showed a relaxant response which was not affected by the treatment with clenbuterol. The radioligand studies showed a reduction in the number of beta-adrenoreceptors after acute and prolonged treatment with clenbuterol in rat uterus. These results suggest that prolonged treatment with clenbuterol caused a desensitization of the relaxant uterine response through beta(2)-adrenoceptors and also showed differences in the recovery of the relaxant response depending on the duration of treatment.
Bramuglia
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Catedra de Farmacologia, Facultad de Farmacia y Bioquimica, Universidad de Buenos Aires, ININFA (CONICET), Junin 956 5 piso, Buenos Aires, 1113, Argentina.
Rubio
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D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000378:metabolism; D000818:Animals; D002976:Clenbuterol / Q000494:pharmacology*; D000242:Cyclic AMP / Q000096:biosynthesis; D004082:Dihydroalprenolol / Q000378:metabolism; D005260:Female; D066298:In Vitro Techniques; D007700:Kinetics; D008565:Membrane Proteins / Q000378:metabolism; D009126:Muscle Relaxation / Q000187:drug effects; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects / Q000378:metabolism; D014590:Uterine Contraction / Q000187:drug effects*; D014599:Uterus / Q000187:drug effects / Q000378:metabolism
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D008565:Membrane Proteins; D018343:Receptors, Adrenergic, beta-2; D004082:Dihydroalprenolol; D000242:Cyclic AMP; D002976:Clenbuterol