Alterations in blood levels of carbohydrate and lipid metabolites and of cyclic AMP mediated by beta1- and beta2-adrenoceptors in beagle dogs: effects of procaterol, a new selective beta2-adrenoceptor agonist

Abstract

The intravenous injection of isoprenaline (10 nmole/kg) into conscious beagle dogs caused significant increases in the blood level of lactate, glucose, FFA, insulin and cyclic AMP. These metabolic alterations induced by isoprenaline were blocked completely by pretreatment of the dog with propranolol (1 mg/kg). Butoxamine (10 mg/kg) antagonized isoprenaline-induced increases in glucose, lactate and insulin, but not the increases in FFA. Practolol (10 mg/kg) diminished the increase in blood FFA very strongly. Salbutamol, which is known to be an agonist of the beta 2-subtype in its bronchomotor and cardiovascular actions, produced marked increases in the blood concentrations of lactate, glucose and insulin but were without effect on the FFA level. Thus metabolic responses of conscious beagle dogs to beta-adrenoceptor agonists appeared to depend differentially on two types of beta-adrenoceptors: beta1-adrenoceptors are largely involved in lipolysis while beta2-adrenoceptors are involved in the regulation of blood glucose metabolism and insulin secretion. A new beta-adrenoceptor agonist, 5-(1-hydroxy-2-isopropylaminobutyl)-8-hydroxycarbostyril hydrochloride hemihydrate (Procaterol), was classified as a beta 2-agonist, because it markedly increased plasma concentrations of glucose, lactate and insulin but increased the plasma level of FFA to a lesser degree. The order of potency of beta2-agonists was procaterol greater than salbutamol greater than trimetoquinol. Metabolic responses of beagle dogs would be useful for appreciating the selectivity and potency of beta-adrenoceptor agonists and antagonists.