Metabolism of isolated kidney tubules. Independent actions of catecholamines on renal cyclic adenosine 3':5'-monophosphate levels and gluconeogenesis

Abstract

Isolated kidney cortex tubules from starved rats have been used to study the actions of catecholamines on renal adenosine 3':5' monophosphate (Ado-3':5'-P) levels and gluconeogenesis. In accordance with previous workers, norepinephrine was found to increase glucose formation from lactate and pyruvate and to a smaller degree from malate, succinate, fumarate and glutamine. The stimulatory effect of 0.5 muM norepinephrine was additive to that of 0.1 mM Ado-3':5-P, indicating an Ado-3':5'-P-independent mechanism of catecholamine action. The effects of parathyroid hormone and oleate on gluconeogenesis were also additive to that of norepinephrine. A comparative study of the actions of different catecholamine derivatives revealed that gluconeogenesis was stimulated in parallel to the alpha-adrenergic potency of the hormones, whereas Ado-3':5'-P levels were increased according to the known beta-stimulatory potency of the agents. Although isoproterenol was by far the most effective in raising Ado-3':5'-P levels, it was without effect on glucose formation from pyruvate, when added at 0.1 muM. At the same concentration, phenylephrine, which had no effect on Ado-3':5'-P levels, was the best stimulator of gluconeogenesis. The alpha-receptor blocking agent phentolamine inhibited the stimulatory effect of catecholamines on gluconeogenesis with a 50 times higher potency than propranolol, a beta-blocking agent. The fact that the stimulatory effect of Ado-3':5'-P was also blocked by propranolol, indicated an unspecific mechanism of action of this substance. The results indicate that the stimulatory effect of catecholamines on renal gluconeogenesis are mediated by an alpha-receptor and that they are independent from the stimulation of renal adenyl cyclase by these agents.