title: Role of β-adrenoceptors, cAMP phosphodiesterase and external Ca2+ on polyamine-induced relaxation in isolated bovine tracheal strips.
abstract: Polyamines relax several smooth muscles and elicit cardiotonic effects in the rat heart via interactions with β-adrenoceptors. The aim of this work was to establish whether β(2)-adrenoceptors were involved in polyamine-relaxation of bovine tracheal strips. Endogenous polyamines displaced the specific radioligand, [(3)H]dihydroalprenolol, but spermine was the most potent. The polyamines elicited an acute transient relaxation, which was independent of β-adrenoceptor activation, followed by a maintained component, which was shown to be dependent on β-adrenoceptor activation because it was antagonized and reversed by propranolol. Polyamines did not alter salbutamol-induced acute relaxation. Polyamines modified the salbutamol-induced long-term effect on airway tone, which was shown by a partial reversal of β-adrenoceptor desensitization. This process was delayed by α-difluoromethylornithine, but spermine increased the latency and time of reversal and decreased receptor desensitization. Putrescine prolonged the time-constant without changes in the desensitization. Spermine, but not putrescine, might block Ca(2+) channels, because it relaxed KCl- or electrical stimulated-contractions, which are related to Ca(2+) influx, and the inhibition of cAMP phosphodiesterase activity. These differences might explain the functional differences observed between putrescine and spermine. Therefore, polyamines may modulate airway smooth muscle tone and interfere with the mechanism of receptor desensitization via several mechanisms involving β(2)-adrenoceptors, Ca(2+) influx and cAMP phosphodiesterase.
authors.affiliation: Pharmacology, Department of Medicine, University of Oviedo, Oviedo 33006, Spain. sanchezf@uniovi.es
authors.forename: Manuel
authors.initials: M
authors.lastname: Sánchez
authors.forename: María J G
authors.initials: MJ
authors.lastname: de Boto
authors.forename: Lorena
authors.initials: L
authors.lastname: Suárez
authors.forename: Clara
authors.initials: C
authors.lastname: Meana
authors.forename: Javier
authors.initials: J
authors.lastname: Bordallo
authors.forename: Lucía
authors.initials: L
authors.lastname: Velasco
authors.forename: Carmen
authors.initials: C
authors.lastname: Bordallo
authors.forename: Begoña
authors.initials: B
authors.lastname: Cantabrana
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism*; D058666:Adrenergic beta-2 Receptor Agonists / Q000494:pharmacology*; D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002417:Cattle; D004082:Dihydroalprenolol / Q000494:pharmacology; D004848:Epithelium / Q000187:drug effects; D066298:In Vitro Techniques; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects; D009955:Ornithine Decarboxylase / Q000378:metabolism; D011073:Polyamines / Q000378:metabolism / Q000494:pharmacology*; D011700:Putrescine / Q000378:metabolism / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D013095:Spermidine / Q000378:metabolism / Q000494:pharmacology; D013096:Spermine / Q000378:metabolism / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects*
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D011073:Polyamines; D011943:Receptors, Adrenergic, beta; D013096:Spermine; D004082:Dihydroalprenolol; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D009955:Ornithine Decarboxylase; D000420:Albuterol; D002118:Calcium; D013095:Spermidine; D011700:Putrescine