Document Detail

Calcitonin gene-related peptide (CGRP)-enhanced non-adrenergic non-cholinergic contraction of guinea-pig proximal colon.
MedLine Citation:
PMID:  7582558     Owner:  NLM     Status:  MEDLINE    
1. We have investigated the effect of calcitonin gene-related peptide (CGRP) on non-adrenergic, non-cholinergic (NANC) excitatory transmission to the longitudinal muscle of the guinea-pig proximal colon. 2. In the presence of atropine (0.3 microM), guanethidine (5 microM), hexamethonium (100 microM) and indomethacin (3 microM), electrical field stimulation (EFS, 1 Hz, 0.3 ms for 10 s) produced tetrodotoxin-(300 nM)-sensitive contractions which were reduced by the combined administration of FK 888 (10 microM) and MEN 10,376 (0.3 microM), to block tachykinin NK1 and NK2 receptors, respectively. Thus, the EFS-induced NANC contractions are a tachykinin-mediated response. 3. CGRP, at concentrations higher than 0.1 nM, caused an increase in the electrically-evoked, NANC contractions in a concentration-dependent manner and at 10 nM produced a maximal effect (pEC50 = 9.20 +/- 0.17, n = 6). 4. 5-Hydroxytryptamine (5-HT, 1-100 nM) also caused an increase in the EFS-induced NANC contractions in a concentration-dependent manner and at 30 nM produced a maximal effect (pEC50 = 8.06 +/- 0.09, n = 4), but calcitonin (10-100 nM) failed to enhance the EFS-induced NANC responses. Moreover, a 5-HT4 receptor antagonist, DAU 6285 (3 microM) abolished the enhancing action of 5-HT (30 nM). 5. The combined administration of FK 888 (10 microM) plus MEN 10,376 (0.3 microM) abolished the enhancement of EFS-induced NANC contractions by CGRP (10 nM), but DAU 6285 (3 microM) had no effect on the enhancement. 6. Human CGRP8-37 (1 microM), a CGRP1 receptor antagonist had no effect on the submaximal enhancement of the electrically-evoked, NANC contractions by CGRP (1 nM).7. CGRP (30 nM) had no effect on contractions evoked by exogenous substance P (0.3-1 nM).8. These results indicate that in the guinea-pig proximal colon, CGRP produced an enhancement ofNANC contraction induced by EFS through prejunctional mechanisms and that the enhancement is mediated by the stimulation of non-CGRP1 receptors located on intramural tachykininergic neurones.Further, the possible contribution of 5-HT to the enhancing effect of CGRP appeared to be negligible.
S Kojima; Y Shimo
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Publication Detail:
Type:  In Vitro; Journal Article    
Journal Detail:
Title:  British journal of pharmacology     Volume:  115     ISSN:  0007-1188     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  1995 Aug 
Date Detail:
Created Date:  1995-12-01     Completed Date:  1995-12-01     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  1290-4     Citation Subset:  IM    
Department of Pharmacology, Dokkyo University School of Medicine, Tochigi, Japan.
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MeSH Terms
Atropine / pharmacology
Calcitonin Gene-Related Peptide / pharmacology*
Colon / drug effects*,  physiology
Electric Stimulation
Guanethidine / pharmacology
Guinea Pigs
Hexamethonium / pharmacology
Indomethacin / pharmacology
Muscle Contraction / drug effects*
Receptors, Adrenergic / drug effects,  physiology
Receptors, Cholinergic / drug effects,  physiology
Serotonin / pharmacology
Substance P / pharmacology
Reg. No./Substance:
0/Receptors, Adrenergic; 0/Receptors, Cholinergic; 33507-63-0/Substance P; 50-67-9/Serotonin; 51-55-8/Atropine; 53-86-1/Indomethacin; 55-65-2/Guanethidine; 60-26-4/Hexamethonium; 83652-28-2/Calcitonin Gene-Related Peptide

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