Modification of renal and tissue cation transport by cholecystokinin octapeptide in the rabbit.

1. Reports that gastric sodium loads cause a greater natriuresis than those administered intravenously, suggest that a gastric or portal sodium monitor exists which releases a humoral natriuretic factor. To determine whether cholecystokinin octapeptide (CCK-8) had direct renal natriuretic effects (and was therefore a candidate for this gut-derived natriuretic factor) we compared the natriuretic response to CCK-8 infused intravenously with that infused directly into the renal artery of six conscious male rabbits. 2. CCK-8 produced a significant log dose-dependent decrease in the fractional excretions of calcium (P less than 0.05) and magnesium (P less than 0.005) and a log dose-dependent increase in fractional sodium excretion (P less than 0.025). The significant decreases in the fractional excretions of calcium and magnesium were accompanied by log dose-dependent falls in their plasma levels (calcium, P less than 0.05, and magnesium, P less than 0.005), indicating movement of calcium and magnesium to extravascular sites. Studies of tissue calcium and magnesium levels in response to CCK-8 infusion showed that calcium accumulated in kidney and skeletal muscle. 3. We conclude that CCK-8 has direct renal natriuretic effects at the tubular level and could be the gut-derived natriuretic factor. In addition to its effects on sodium excretion, CCK-8 causes renal retention and increased gut absorption of calcium and magnesium with movement of these ions to extravascular sites.