The effects of IAPP and CGRP on guinea pig tracheal smooth muscle in vitro

Abstract

Neither the novel peptide, islet amyloid polypeptide (IAPP), nor its homologue, calcitonin gene-related peptide (CGRP), contracted guinea pig isolated trachea (GPT), but on preparations contracted with KCl (40 mM), both caused concentration-related relaxation (1 nM-3 microM). Relaxant curves to both were shallow and slow in development, with clear maxima not being obtained. The protease inhibitors, phosphoramidon (1 microM), leupeptin (50 microM), bestatin (100 microM), soya bean trypsin inhibitor (1 microM), and aprotinin (5 microM), together had no effect on relaxations to CGRP, but depressed those to IAPP. Aprotinin appeared to be responsible for this depression. The specific CGRP antagonist, CGRP(8-37), 1-10 microM, had no effect on relaxations to either peptide. These findings demonstrate that IAPP relaxes GPT in a similar manner to CGRP.