Effect of compound D-600 (methoxyverapamil) on gluconeogenesis and on acceleration of the process by α-adrenergic stimuli in rat kidney tubules

Abstract

1. Tubule fragments were isolated from renal cortex of fed rats and glucose formation was measured after incubation with 5 mM-sodium lactate. 20 Compound D-600 (10-100 microM) decreased gluconeogenesis from lactate. This inhibition of the process by compound D-600 increased with increasing extracellular Ca2+ concentration, was overridden by noradrenaline and diminished by starvation for 24 h. 3. Inhibition of lactate-supported gluconeogenesis by compound D-600 was not prevented by the alpha 1-adrenoceptor antagonist thymoxamine. 4. Compound D-600 had little effect on gluconeogenesis from 2-oxoglutarate and increased gluconeogenesis from succinate. 5. Compound D-600 opposed stimulation of gluconeogenesis by noradrenaline or oxymetazoline (a selective alpha-adrenoceptor agonist) in a manner suggesting that compound D-600 is an alpha-adrenoceptor blocker. Oxymetazoline was more sensitive than noradrenaline to blockade by both compound D-600 and by the conventional alpha-adrenoceptor antagonist phentolamine. Noradrenaline became more sensitive to blockade by compound D-600 when extracellular Ca2+ was decreased. 6. Compound D-600 did not block stimulation of gluconeogenesis by angiotensin or cyclic AMP.

Carnitine palmitoyltransferase I

“…As shown in Fig. I , the curve of transferase I activity versus palmitoyl-CoA appears hyperbolic in agreement with Mc Garry et al [ I q and Bremer [18] but contrary to Saggerson and Carpenter [19], giving a K , of 28.1 pM and a V of 3.33 nmol x min-' x mg protein-', values in the same order of magnitude than those reported by all these authors. 3 h after administration, GalN induced an inhibition of palmitoyl-L-[Me-3H]carnitine synthesis from palmitoyl-CoA and [Me-'Hlcarnitine.…”

“…This point was already suggested in our previous report [l]. Recently, evidence has been offered that fatty acid oxidation is controlled by the hepatic level of malonyl-CoA [19,27,28]. From a physiological standpoint, it can be assumed that, due to its localization, only transferase I is exposed to malonyl-CoA, which is formed in the cytosolic compartment of the hepatocyte.…”

[Leu]enkephalin stimulates carbohydrate metabolism in isolated hepatocytes and kidney tubule fragments by interaction with angiotensin II receptors

“…3 shows that addition of 10-5 M-[Leu]enkephalin to isolated kidney tubule fragments significantly increased glucose synthesis from 5 mM-pyruvate over the first 45 min of the incubation. The effect of the opioid peptide was comparable to that of either adrenaline or angiotensin II, other agents which are known to stimulate gluconeogenesis in this system (Guder & Rupprecht, 1975;MacDonald & Saggerson, 1977;Guder, 1979;Saggerson & Carpenter, 1979;Saggerson & Carpenter, 1980;Kessar & Saggerson, 1980), the percentage stimulation being 420, 42 % and 350 for [Leu]enkephalin, adrenaline and angiotensin II respectively. In contrast to the effects of the other two agents, the response to the opioid peptide was not apparent over the last 15 min of the incubation.…”

“…To determine whether the cross-reactivity of opioid peptides with angiotensin II receptors was a property of the liver or whether it may be a more general phenomenon, we investigated the possibility that enkephalins influence carbohydrate metabolism in the kidney cortex tubules, as renal gluconeogenesis is also enhanced by angiotensin II (Guder, 1979;Saggerson & Carpenter, 1980). Fig.…”