Alterations in blood levels of carbohydrate and lipid metabolites and of cyclic AMP mediated by β1- and adrenoceptors in beagle dogs: Effects of procaterol, a new selective β2-adrenoceptor agonist

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 β2-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 β-adreboceptor agonists appeared to depend differentially on two types of β-adrenoceptors: β1-adrenoceptors are largely involved in lipolysis while β2-adrenoceptors are involved in the regulation of blood glucose metabolism and insulin secretion. A new β-adrenoceptor agonist, 5-(1-hydroxy-2-isopropylaminobutyl)-8-hydroxycarbostyril hydrochloride hemihydrate (Procaterol), was classified as a β2- 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 β2-agonists was procaterol salbutamol trimetoquinol. Metabolic responses of beagle dogs would be useful for appreciating the selectivity and potency of β-adrenoceptor agonists and antagonists.