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

Autor: Yasuko Yamazaki, Tadashi Takewaki, Kaori Fujinami, Akikazu Fujita, Tadayoshi Takeuchi, Fumiaki Hata, Kazunori Mukai, Tamotsu Negoro
Rok vydání: 2003
Předmět:
Zdroj: Regulatory peptides. 118(1-2)
ISSN: 0167-0115
Popis: 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.
Databáze: OpenAIRE