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, glutamate and glutamine. The stimulatory effect of 0.5 μM 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 α-adrenergic potency of the hormones, whereas Ado-3′: 5′-P levels were increased according to the known β-stimulatory potency of the agents. Although iso-proterenol 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 μM. At the same concentration, phenylephrine, which had no effect on Ado-3′:5′-P levels, was the best stimulator of gluconeogenesis. The α-receptor blocking agent phentolamine inhibited the stimulatory effect of catecholamines on gluconeogenesis with a 50 times higher potency than propranolol, a,β-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 a-receptor and that they are independent from the stimulation of renal adenyl cyclase by these agents.