Changes in mechanism of PACAP-induced relaxation in longitudinal muscle of the distal colon of Wistar rats with age

Mechanisms of relaxation of longitudinal muscle of the distal colon induced by exogenously added pituitary adenylate cyclase activating peptide (PACAP) were studied in 2- to 30-week-old Wistar rats. Exogenous PACAP induced very significant relaxation of the longitudinal muscle in 2-week-old rats, bu...

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Bibliographic Details
Published in:Regulatory peptides 2004-04, Vol.118 (1), p.1-9
Main Authors: Takeuchi, Tadayoshi, Yamazaki, Yasuko, Negoro, Tamotsu, Fujinami, Kaori, Mukai, Kazunori, Fujita, Akikazu, Takewaki, Tadashi, Hata, Fumiaki
Format: Article
Language:English
Subjects:
Age Factors
Aging
Animals
Apamin
Biological and medical sciences
Colon - drug effects
Colon - physiology
Cyclic AMP
Female
Fundamental and applied biological sciences. Psychology
Male
Muscle Relaxation - drug effects
Muscle, Smooth - drug effects
Muscle, Smooth - physiology
Neuropeptides - pharmacology
Nitric oxide
Pituitary Adenylate Cyclase-Activating Polypeptide
Rats
Rats, Wistar
SK channel
Tyrosine kinase
Vertebrates: endocrinology
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Summary:Mechanisms of relaxation of longitudinal muscle of the distal colon induced by exogenously added pituitary adenylate cyclase activating peptide (PACAP) were studied in 2- to 30-week-old Wistar rats. Exogenous PACAP induced very significant relaxation of the longitudinal muscle in 2-week-old rats, but this effect decreased significantly with age. The cyclic AMP–cyclic AMP-dependent protein kinase (PKA) pathway and the tyrosine kinase–small conductance Ca 2+-activated K + channel (SK channel) pathway were found to be involved in the mechanism of PACAP-induced relaxation. In 2-week-old rats, PACAP-induced relaxation was significantly inhibited by tetrodotoxin (TTX). Since relaxation was also significantly inhibited by N G-nitro- l-arginine ( N 5-nitro-amidino- l-2,5-diamino-pentanoic acid: l-NOARG), the neurogenic effect of PACAP seems to be mediated mainly through nitric oxide neurons. In 8-week-old rats, l-NOARG and TTX had little effect on PACAP-induced relaxation, suggesting that the relaxant effect in 8-week-old rats is a direct action on longitudinal smooth muscle cells. Changes in the mechanisms of PACAP-induced relaxation with age were examined in the distal colon in relation to changes in the neurogenic and the direct effects of PACAP. The neurogenic effect in the exogenous PACAP-induced relaxation of the longitudinal muscle of the Wistar rat distal colon is dominant in tissue isolated from 2-week-old and lost in tissue isolated from 8-week-old rats.
ISSN:0167-0115
1873-1686
DOI:10.1016/j.regpep.2003.10.033