Evidence of splanchnic-brain signaling in inhibition of ingestive behaviorby middle molecules

Anorexia, nausea, and vomiting are common symptoms of uremic intoxication. Fractions in the middle molecule weight range, isolated from normal urine a nd uremic plasma ultrafiltrate, inhibit ingestive behavior in the rat. To i nvestigate their site of action and specificity, male rats were injected in traperitoneally, intravenously, or intracerebroventricularly with concentra ted fractions of uremic plasma ultrafiltrate or normal urine (molecular wei ght range: 1.0 to 5.0 kD) and tested for ingestive and sexual behavior. An intraperitoneal injection of 0.5 ml of urine fraction (10:1) or 2.0 ml of u remic plasma ultrafiltrate fraction (25:1) inhibited carbohydrate intake by 76.3 and 45.9%, respectively, but an intravenous injection had no effect. However, intravenous injection of higher doses inhibited carbohydrate inges tion. An intracerebroventricular injection of 5 or 10 mu l of urine (20:1) middle molecule fraction inhibited carbohydrate intake by 13.4 and 41.6%, r espectively. An injection of 5 or 10 mu l of uremic plasma ultrafiltrate (1 25:1) middle molecule fraction inhibited carbohydrate intake by 22.6 and 49 .5%, respectively. Injections of the corresponding fraction from normal pla sma ultrafiltrate had no effect. Injection of urine or uremic plasma ultraf iltrate middle molecule fractions did not affect the display of sexual beha vior. These results suggest that middle molecule fractions from uremic plas ma ultrafiltrate or normal urine act in the splanchnic region and/or brain to inhibit food intake and that the effect is specific for ingestive behavi or.