Amylin compared with calcitonin: competitive binding studies in rat brain and antinociceptive activity.
Binding studies for rat amylin (AMY) and salmon calcitonin (sCT) were performed on rat membranes prepared from pons and medulla oblongata of rats. The aim was to see whether specific binding sites for AMY and/or for sCT present in these areas could be relevant to some of the biological activities of the two peptides. Binding sites specific for [125I]AMY are present in the pons-medulla of rat brain as AMY, but not sCT, was able to displace radiolabeled AMY binding with an IC50 = 3.7+/-0.5x10(-10) M. In contrast, binding of [125I]sCT was displaced by both sCT and AMY, although with different potencies, the IC50 for sCT being 1+/-0.1x10(-11) M, and for AMY, 1.8+/-0.08x10(-7) M. The functional significance of the presence of these binding sites was evaluated in two different nociceptive tests, hot-plate and tail-flick. In the tail-flick test neither AMY (5-10 microg/rat, i.c.v.) nor sCT (10 microg/rat i.c.v.) showed antinociceptive activity, whereas in the hot-plate test AMY (10 microg/rat, i.c.v.) significantly increased the response latencies as did sCT (250 ng/rat, i.c.v.). These results demonstrated that a 40-fold greater dose of AMY is necessary to produce a comparable antinociceptive effect to that exerted by sCT. These findings are in accordance with the low affinity of AMY for sCT binding sites in rat pons-medulla. It is therefore suggested that the central inhibitory activity of AMY on pain perception involves interaction with sCT receptors whereas the selective AMY binding sites subserve other (as yet unknown) functions.
Sibilia
V
V
Department of Pharmacology, Chemotherapy and Medical Toxicology, University of Milano, Milan, Italy. valeria.sibilia@unimi.it
Pagani
F
F
Lattuada
N
N
Rapetti
D
D
Guidobono
F
F
Netti
C
C
D000682:Amyloid / Q000378:metabolism* / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D002116:Calcitonin / Q000378:metabolism* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D058228:Islet Amyloid Polypeptide; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism; D009619:Nociceptors / Q000187:drug effects*; D011149:Pons / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012474:Salmon
D000682:Amyloid; D058228:Islet Amyloid Polypeptide; D002116:Calcitonin