Amylin receptors mediate the anorectic action of salmon calcitonin (sCT).
The teleost salmon calcitonin (sCT), but not mammalian CT, shows similar biologic actions in the skeletal muscle as amylin and calcitonin gene-related peptide (CGRP). The peptides have also been shown to reduce food intake in rams. Because sCT, but not amylin, binds irreversibly to amylin binding sites, the aim of the present study was to compare the anorectic potency of both peptides. To determine whether sCT reduces food intake through interaction with amylin binding sites, we also tested whether appropriate antagonists (CORP 8-37, AC 187) attenuate the anorectic effect of sCT. Finally, we wanted to know whether rat calcitonin (rCT) and sCT reduce food intake to the same extent. Peptides were injected intraperitoneally at dark onset in 24 h food-deprived rats. At doses of 5 or 0.5 microg/kg, the anorectic effect of sCT was more potent and lasted much longer (e.g. 5 microg/kg: sCT > 10 h; amylin approx. 2 h) than that of amylin. Both CORP 8-37 and AC 187 (10 microg/kg) markedly reduced the anorectic action of sCT (0.5 microg/kg). In contrast to sCT, rCT (0.5 microg/kg) had no effect on food intake. It is concluded that sCT s anorectic effect is partly mediated by amylin receptors. Irreversible binding of sCT to amylin receptors may lead to a stronger and prolonged effect in comparison to amylin due to a sustained activation of the binding sites. Similar to other actions of CTs, the anorectic potency of sCT in rats was higher than that of mammalian (rat) CT. This agrees with binding profiles of amylin, sCT, and rCT at amylin binding sites as observed in in vitro studies.
Lutz
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Institute of Veterinary Physiology, University of Zürich, Winterthurerstrasse 260, 8057, Zürich, Switzerland. tomlutz@vetphys.unizh.ch
Tschudy
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Rushing
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Scharrer
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D000682:Amyloid / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D001067:Appetite Depressants / Q000494:pharmacology*; D001665:Binding Sites; D002116:Calcitonin / Q000494:pharmacology*; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D004435:Eating / Q000187:drug effects; D058228:Islet Amyloid Polypeptide; D018482:Muscle, Skeletal / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D058287:Receptors, Islet Amyloid Polypeptide; D018000:Receptors, Peptide / Q000378:metabolism*; D012474:Salmon; D013997:Time Factors
D000682:Amyloid; D001067:Appetite Depressants; D058228:Islet Amyloid Polypeptide; D010446:Peptide Fragments; D010455:Peptides; D058287:Receptors, Islet Amyloid Polypeptide; D018000:Receptors, Peptide; C058636:calcitonin gene-related peptide (8-37); C087166:AC 187; D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide