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Pituitary Adenylate Cyclase-activating Polypeptide Inhibits Pacemaker Activity of Colonic Interstitial Cells of Cajal
- Source :
- The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology
- Publication Year :
- 2015
- Publisher :
- The Korean Physiological Society and The Korean Society of Pharmacology, 2015.
-
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-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.
- Subjects :
- Pharmacology
endocrine system
medicine.medical_specialty
Colon
Pituitary adenylate cyclase-activating polypeptide (PACAP)
Physiology
business.industry
Adenylate kinase
Membrane hyperpolarization
Hyperpolarization (biology)
Cyclase
Interstitial cell of Cajal
Pacemaker potential
Electrophysiology
symbols.namesake
Endocrinology
ATP-sensitive K+ (KATP) channels
Internal medicine
medicine
symbols
Original Article
Channel blocker
business
Interstitial cells of Cajal (ICC)
hormones, hormone substitutes, and hormone antagonists
Subjects
Details
- ISSN :
- 20933827 and 12264512
- Volume :
- 19
- Database :
- OpenAIRE
- Journal :
- The Korean Journal of Physiology & Pharmacology
- Accession number :
- edsair.doi.dedup.....1ef4a89f58bce87eb5a4a24d66ca1cf4