THE EFFECTS OF IAPP AND CGRP ON GUINEA-PIG TRACHEAL SMOOTH-MUSCLE IN-VITRO

被引:10
作者
BHOGAL, R [1 ]
SHELDRICK, RLG [1 ]
COLEMAN, RA [1 ]
SMITH, DM [1 ]
BLOOM, SR [1 ]
机构
[1] GLAXO GRP RES LTD,DIV BIOL,WARE SG12 0DP,HERTS,ENGLAND
基金
英国医学研究理事会;
关键词
ISLET AMYLOID POLYPEPTIDE (IAPP); CALCITONIN GENE-RELATED PEPTIDE (CGRP); CGRP(8-37); GUINEA PIG TRACHEA; AIRWAY SMOOTH MUSCLE; RELAXATION; PROTEASE INHIBITORS;
D O I
10.1016/0196-9781(94)90148-1
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 mu M). Relaxant curves to both were shallow and slow in development, with clear maxima not being obtained. The protease inhibitors, phosphoramidon (1 mu M), leupeptin (50 mu M), bestatin (100 mu M), soya bean trypsin inhibitor (1 mu M) and aprotinin (5 mu M), 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 mu M, had no effect on relaxations to either peptide. These findings demonstrate that IAPP relaxes GPT in a similar manner to CGRP.
引用
收藏
页码:1243 / 1247
页数:5
相关论文
共 21 条
[1]   AIRWAY NEUROPEPTIDES AND ASTHMA [J].
BARNES, PJ .
TRENDS IN PHARMACOLOGICAL SCIENCES, 1987, 8 (01) :24-27
[2]   INVESTIGATION AND CHARACTERIZATION OF BINDING-SITES FOR ISLET AMYLOID POLYPEPTIDE IN RAT MEMBRANES [J].
BHOGAL, R ;
SMITH, DM ;
BLOOM, SR .
ENDOCRINOLOGY, 1992, 130 (02) :906-913
[3]  
BHOGAL R, 1992, BRIT J PHARMACOL, V107, pP35
[4]   CALCITONIN GENE-RELATED PEPTIDE IS A POTENT VASODILATOR [J].
BRAIN, SD ;
WILLIAMS, TJ ;
TIPPINS, JR ;
MORRIS, HR ;
MACINTYRE, I .
NATURE, 1985, 313 (5997) :54-56
[5]   CARBAMYLCHOLINE-INDUCED AND 5-HYDROXYTRYPTAMINE-INDUCED CONTRACTION IN RAT ISOLATED AIRWAYS - INHIBITION BY CALCITONIN GENE-RELATED PEPTIDE [J].
CADIEUX, A ;
LANOUE, C ;
SIROIS, P ;
BARABE, J .
BRITISH JOURNAL OF PHARMACOLOGY, 1990, 101 (01) :193-199
[6]   OCCURRENCE, DISTRIBUTION AND ONTOGENY OF CGRP IMMUNOREACTIVITY IN THE RAT LOWER RESPIRATORY-TRACT - EFFECT OF CAPSAICIN TREATMENT AND SURGICAL DENERVATIONS [J].
CADIEUX, A ;
SPRINGALL, DR ;
MULDERRY, PK ;
RODRIGO, J ;
GHATEI, MA ;
TERENGHI, G ;
BLOOM, SR ;
POLAK, JM .
NEUROSCIENCE, 1986, 19 (02) :605-+
[7]   CALCITONIN GENE-RELATED PEPTIDE RECEPTOR ANTAGONIST HUMAN CGRP-(8-37) [J].
CHIBA, T ;
YAMAGUCHI, A ;
YAMATANI, T ;
NAKAMURA, A ;
MORISHITA, T ;
INUI, T ;
FUKASE, M ;
NODA, T ;
FUJITA, T .
AMERICAN JOURNAL OF PHYSIOLOGY, 1989, 256 (02) :E331-E335
[8]  
COLEMAN RA, 1987, PROSTAGLANDINS RELAT, P267
[9]   SIMULTANEOUS ANALYSIS OF FAMILIES OF SIGMOIDAL CURVES - APPLICATION TO BIOASSAY, RADIOLIGAND ASSAY, AND PHYSIOLOGICAL DOSE-RESPONSE CURVES [J].
DELEAN, A ;
MUNSON, PJ ;
RODBARD, D .
AMERICAN JOURNAL OF PHYSIOLOGY, 1978, 235 (02) :E97-E102
[10]  
DENNIS T, 1989, J PHARMACOL EXP THER, V251, P718