Amylin compared with calcitonin: competitive binding studies in rat brain and antinociceptive activity

Binding studies for rat amylin (AMY) and salmon calcitonin (sCT) were perfo rmed on rat membranes prepared from pens and medulla oblongata of rats. The aim was to see whether specific binding sites for AMY and/or for sCT prese nt in these areas could be relevant to some of the biological activities of the two peptides. Binding sites specific for [I-125]AMY are present in the pons-medulla of rat brain as AMY, but not sCT, was able to displace radiol abeled AMY binding with an IC50 = 3.7 +/- 0.5 x 10(-10) M. In contrast, bin ding of [I-125]sCT was displaced by both sCT and AMY, although with differe nt potencies, the IC50 for sCT being 1 +/- 0.1 X 10(-11) M, and for AMY, 1. 8 +/- 0.08 X 10(-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 mu g/rat, i.c.v.) nor sCT (10 mu g/rat i.c.v.) showed antinociceptive activity, whereas in th e hot-plate test AMY (10 mu g/rat, i.c.v.) significantly increased the resp onse 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 ant inociceptive effect to that exerted by sCT. These findings are in. accordan ce 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 pa in perception involves interaction with sCT receptors whereas the selective AMY binding sites subserve other (as yet unknown) functions. (C) 2000 Publ ished by Elsevier Science B.V. All rights reserved.