Pituitary Adenylate Cyclase-activating Polypeptide Inhibits Pacemaker Activity of Colonic Interstitial Cells of Cajal.
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-α]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.
Department of Physiology, Chonnam National University Medical School, Gwangju 501-757, Korea.
Mei Jin
MJ
Wu
Department of Pathology, College of Medicine, Chosun University, Gwangju 501-759, Korea.
Keun Hong
KH
Kee
Department of Internal Medicine, College of Medicine, Chosun University, Gwangju 501-759, Korea.
Jisun
J
Na
Department of Internal Medicine, College of Medicine, Chosun University, Gwangju 501-759, Korea.
Seok Won
SW
Kim
Department of Dermatology, Hallym University Dongtan Sacred Heart Hospital, Hwaseong 445-907, Korea.
Youin
Y
Bae
Department of Physiology, College of Medicine, Chosun University, Gwangju 501-759, Korea.
Dong Hoon
DH
Shin
Department of Physiology, College of Medicine, Chosun University, Gwangju 501-759, Korea.
Seok
S
Choi
Department of Physiology, College of Medicine, Chosun University, Gwangju 501-759, Korea.
Jae Yeoul
JY
Jun
Department of Physiology, Chonnam National University Medical School, Gwangju 501-757, Korea.
Han-Seong
HS
Jeong
Department of Physiology, Chonnam National University Medical School, Gwangju 501-757, Korea.
Jong-Seong
JS
Park
ATP-sensitive K+ (KATP) channels; Colon; Interstitial cells of Cajal (ICC); Pituitary adenylate cyclase-activating polypeptide (PACAP)