Intracerebroventricular injection of 125I-salmon calcitonin in rats: fate, anorexia and hypocalcemia.
Intracerebroventricular (i.c.v.) injection of 19 pmol/rat or more of salmon calcitonin (sCT) or iodinated sCT suppressed spontaneous intake of food and water in a dose-dependent manner. Tail-whipping was a peculiar behavior which concomitantly developed, but no analgesia ensued from the doses tested (up to 62 pmol/rat). It was examined how the rise and fall pattern of these behavioral effects would correlate with the dispositional pattern of 125I-sCT. When the radioactive peptide was injected in anorectic doses via the i.c.v. route, the radioactivity was found to distribute throughout the brain, but not uniformly. In rats which showed a marked anorexia and tail-whipping behavior, distribution occurred in such a manner that it could be interpreted to reflect the regional and subcellular distribution pattern of sCT-specific binding sites. Even 3 hr after injection, the hypothalamus, the smallest region, retained the highest radioactivity corresponding to about 1% of the dose and at least one half of which was identified as the intact iodo-sCT. To be noted is the finding that sCT injected centrally will quickly enter the systemic circulation and peripherally induced long-lasting hypocalcemia, since the anorectic dose of sCT is considerably higher than the dose needed for the peripheral effect. It is concluded that most of the sCT after i.c.v. injection leaks into the systemic circulation, but the rest is retained rather selectively around the receptor in hypothalamic nuclei for a long time, leading to day-long suppression of feeding and drinking behavior.
D000818:Animals; D001067:Appetite Depressants; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D002116:Calcitonin / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D006996:Hypocalcemia / Q000139:chemically induced*; D007031:Hypothalamus / Q000378:metabolism; D007276:Injections, Intraventricular; D007457:Iodine Radioisotopes; D007700:Kinetics; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013347:Subcellular Fractions / Q000378:metabolism
D001067:Appetite Depressants; D007457:Iodine Radioisotopes; C028815:salmon calcitonin; D002116:Calcitonin