Gastrin and cholecystokinin (CCK) make up a family of important gastrointestinal and central nervous system peptide hormones and neurotransmitters. In the gastrointestinal system, these peptides become elevated in response to a meal and function to stimulate secretion and motility necessary to regulate the digestive process. It has been observed for more than a century that ingestion of a meal results in acute changes in renal function necessary to handle the absorbed nutrients. We have previously shown in rat that receptors for gastrin (cholecystokinin type B receptors, CCKBR) are present in proximal tubules of the kidney and that gastrin, elevated by either a gavaged meal or direct renal infusion stimulate an increase in urinary Na+ excretion and urine volume that was inhibited by the CCKBR/gastrin receptor-specific antagonist, L-365,260. Gastrin stimulated excretion of sodium and water and its reversal by L-365,260 were paralleled by CCKBR/gastrin mediated inhibition and reversal of inhibition of renal tubular Na+-K+-ATPase activity, respectively. To confirm these findings in another species and unequivocally demonstrate that the effect of a meal on subsequent renal handling of salt and water is mediated by gastrin and not other potential mediators also known to be elevated by a meal, we have used gastrin deficient (gastrin gene deletion) mice to study the effect of a meal on renal handling of salt and water. In gastrin deficient mice, a gavaged meal of rat chow had no effect on renal function. However, in age and sized matched controls of the same background strain, a gavaged meal resulted in an increase in urine volume and sodium excretion that was not observed with a control gavage of just sodium and water equivalent to the gavaged meal. These results unequivocally demonstrate that gastrin acting at renal tubular gastrin receptors is the principle and direct link between digestion and renal function.
