title: Changes in mechanism of PACAP-induced relaxation in longitudinal muscle of the distal colon of Wistar rats with age.
abstract: 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 Ca2+-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 NG-nitro-L-arginine (N5-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.
authors.affiliation: Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, Osaka Prefecture University, Sakai 599-8531, Japan.
authors.forename: Tadayoshi
authors.initials: T
authors.lastname: Takeuchi
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Yamazaki
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Negoro
authors.forename: Kaori
authors.initials: K
authors.lastname: Fujinami
authors.forename: Kazunori
authors.initials: K
authors.lastname: Mukai
authors.forename: Akikazu
authors.initials: A
authors.lastname: Fujita
authors.forename: Tadashi
authors.initials: T
authors.lastname: Takewaki
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Hata
mesh_terms: D000367:Age Factors; D000818:Animals; D003106:Colon / Q000187:drug effects* / Q000502:physiology; D005260:Female; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D009479:Neuropeptides / Q000494:pharmacology*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051381:Rats; D017208:Rats, Wistar
chemical_list: C495403:Adcyap1 protein, rat; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide