Pituitary Adenylate Cyclase-activating Polypeptide Inhibits Pacemaker Activity of Colonic Interstitial Cells of Cajal.
10.4196/kjpp.2015.19.5.435
- Author:
Mei Jin WU
1
;
Keun Hong KEE
;
Jisun NA
;
Seok Won KIM
;
Youin BAE
;
Dong Hoon SHIN
;
Seok CHOI
;
Jae Yeoul JUN
;
Han Seong JEONG
;
Jong Seong PARK
Author Information
1. Department of Physiology, Chonnam National University Medical School, Gwangju 501-757, Korea. parkjs@jnu.ac.kr
- Publication Type:Original Article
- Keywords:
ATP-sensitive K+ (K(ATP)) channels;
Colon;
Interstitial cells of Cajal (ICC);
Pituitary adenylate cyclase-activating polypeptide (PACAP)
- MeSH:
8-Bromo Cyclic Adenosine Monophosphate;
Animals;
Cell Membrane;
Colon*;
Cyclic AMP;
Glyburide;
Interstitial Cells of Cajal*;
Membranes;
Mice;
NG-Nitroarginine Methyl Ester;
Pituitary Adenylate Cyclase-Activating Polypeptide*
- From:The Korean Journal of Physiology and Pharmacology
2015;19(5):435-440
- CountryRepublic of Korea
- Language:English
-
Abstract:
This study aimed to investigate the effect of pituitary adenylate cyclase-activating peptide (PACAP) on the pacemaker activity of interstitial cells of Cajal (ICC) in mouse colon and to identify the underlying mechanisms of PACAP action. Spontaneous pacemaker activity of colonic ICC and the effects of PACAP were studied using electrophysiological recordings. Exogenously applied PACAP induced hyperpolarization of the cell membrane and inhibited pacemaker frequency in a dose-dependent manner (from 0.1 nM to 100 nM). To investigate cyclic AMP (cAMP) involvement in the effects of PACAP on ICC, SQ-22536 (an inhibitor of adenylate cyclase) and cell-permeable 8-bromo-cAMP were used. SQ-22536 decreased the frequency of pacemaker potentials, and cell-permeable 8-bromo-cAMP increased the frequency of pacemaker potentials. The effects of SQ-22536 on pacemaker potential frequency and membrane hyperpolarization were rescued by co-treatment with glibenclamide (an ATP-sensitive K+ channel blocker). However, neither N(G)-nitro-L-arginine methyl ester (L-NAME, a competitive inhibitor of NO synthase) nor 1H-[1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one (ODQ, an inhibitor of guanylate cyclase) had any effect on PACAP-induced activity. In conclusion, this study describes the effects of PACAP on ICC in the mouse colon. PACAP inhibited the pacemaker activity of ICC by acting through ATP-sensitive K+ channels. These results provide evidence of a physiological role for PACAP in regulating gastrointestinal (GI) motility through the modulation of ICC activity.
