Importance of amino acids on vasopressin-stimulated water flow.

Abstract

The presence of several naturally occurring amino acids in the serosal bath of toad urinary bladder significantly alters the hydrosmotic response of this tissue to vasopressin. We found that histidine, glutamate, and lysine increase vasopressinstimulated water flow by 75%, 60%, and 43%, respectively. In contrast, alanine did not alter vasopressin-stimulated water flow, whereas glutamine decreased it by 25%. The effect of each amino acid represents intracellular events because their effects on theophylline-stimulated water flow were similar to those found with vasopressin. However, the site of action of amino acids varied, with some operating at steps before and others at steps after cyclic AMP generation. The fact that the metabolically inactive D-histidine and D-glutamate are as effective as their metabolically active L-counterparts suggests that the action of amino acids depends upon some physicochemical properties of their molecules. The ability of amino acids to influence the hydrosmotic effects of vasopressin was shown to be independent of prostaglandin generation, ionic composition, and molecular charge.In the case of histidine, we were able to obtain some understanding of the mechanism responsible for its action. We first showed that the effect of histidine does not depend upon its metabolism. In addition to D-histidine being as effective as the metabolically active L-histidine, we also showed that histidine is effective when its metabolism is abolished by low ambient temperature and also when its incorporation into proteins was prevented by cycloheximide. These findings suggest that histidine operates through some physicochemical property localized on its molecule. We were able to show that this property resides on the imidazole part of histidine. Imidazole, similar to histidine, increases vasopressin-stimulated water flow. Methylation of histidine on the imidazole ring completely abolished its effectiveness in increasing vasopressin-stimulated water flow. In contrast, methylation of histidine at the side chain increased vasopressin action similar to that found for histidine.We provide evidence that the physicochemical property of the imidazole ring of histidine is that of chelating Zn++

L-histidine augments the response to 1-deamino-8-D-arginine vasopressin in Brattleboro homozygous (di/di) rats.

“…Addition of histidine to the diet increased plasma histidine from 29±2 mM, n = 5 (control diet) to 35±3, n = 5 (1% histidine) to 47±4, n = 5 (5% histidine). (9,18). The lesser increase of urine osmolality with D-histidine may reflect decreased intestinal absorption of the amino acid, given the stereospecificity of uptake of amino acids in the intestine.…”

“…This is theoretically not surprising since histidine alters the production and function of prostaglandins (18), cAMP, and cytoskeleton (9), all important constituents for the function of peptide hormones in general. Indeed, a more global role for histidine and other amino acids in modulating the action of peptide hormones has been suggested (9). Our present studies therefore could lead to meaningful research to identify the naturally occurring amino acids as modulatory systems in the action of hormones.…”

“…Several amino acids are known to alter vasopressin-stimulated water flow in the toad bladder (9). Vasopressin-stimulated water flow is increased by L-histidine, L-glutamate, and L-lysine and decreased by L-glutamine.…”

“…This would then allow formation of microtubules which are important in the action of vasopressin (9).…”

The Impact of Malnutrition on Kidney Function

“…In vitro studies indicate that amino acids such as histidine, glutamate, and lysine can enhance the hydroosmotic response to vasopressin [43]. Thus, it is possible that decreases in the levels of free amino acids in severe protein-calorie malnutrition may further impair renal concentrating capacity.…”