Regulation of small intestinal transit by central nervous calcitonin receptor.
Salmon calcitonin (sCT) suppresses small intestinal transit (SIT) or motility, but the mechanism is not well understood. Bolus s. c. administration of a pharmacologic dose of sCT (140 IU/kg) to mice significantly decreased plasma calcium and phosphorus, and suppressed SIT from 1 to 8 h for plasma calcium and phosphorus or 20 h for SIT (respective maximal effects were seen at 5 h, between 2 and 8 h, and between 1 and 5 h). Significant SIT inhibition did not occur at doses smaller than 140 IU/kg. Reverse transcription-polymerase chain reactions and Southern analysis demonstrated high levels of calcitonin 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, testis, or heart. Specific binding of [125I] sCT was demonstrated in the diencephalon. Intracerebroventricular (i.c.v.) administration of sCT inhibited 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 results suggest that sCT binds to receptors in the central nervous system and inhibits small bowel transit.
Hamada
S
S
Department of Biochemistry, Ohu University School of Dentistry, Koriyama, Japan.
Kawane
T
T
Akeno
N
N
Igarashi
H
H
Horiuchi
N
N
D000818:Animals; D002118:Calcium / Q000097:blood; D002490:Central Nervous System / Q000502:physiology*; D015536:Down-Regulation; D005772:Gastrointestinal Transit; D007276:Injections, Intraventricular; D007279:Injections, Subcutaneous; D007421:Intestine, Small / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010710:Phosphates / Q000097:blood; D018003:Receptors, Calcitonin / Q000502:physiology*
D010710:Phosphates; D018003:Receptors, Calcitonin; D002118:Calcium