Regulation of small intestinal transit by central nervous calcitonin receptor

Salmon calcitonin (sCT) suppresses small intestinal transit (SIT) or motili ty, but the mechanism is not well understood. Bolus s.c. administration of a pharmacologic dose of sCT (140 IU/kg) to mice significantly decreased pla sma calcium and phosphorus, and suppressed SIT from 1 to 8 h for plasma cal cium and phosphorus or 10 h for SIT (respective maximal effects were seen a t 5 h, between 2 and 8 h, and between 1 and 5 h). Significant SIT inhibitio n did not occur at doses smaller than 140 IU/kg. Reverse transcription-poly merase chain reactions and Southern analysis demonstrated high levels of ca lcitonin receptor mRNA in diencephalon and lung, moderate levels of mRNA in cerebellum, kidney, and muscle, and barely detectable amounts in cerebral cortex and thymus. No message was detectable in duodenum, jejunum, liver, t estis, or heart. Specific binding of [I-125] sCT was demonstrated in the di encephalon. Intracerebroventricular (i.c.v.) administration of sCT inhibite d SIT time- and dose-dependently, Maximal inhibition was obtained at a dose of 4 IU/kg, 20 min after injection. Pretreatment with sCT (140 IU/kg s.c.) completely abolished inhibition of SIT by i.c.v. sCT (4 IU/kg). These resu lts suggest that sCT binds to receptors in the central nervous system and i nhibits small bowel transit.