PGE2 Regulates Pacemaker Currents through EP2-Receptor in Cultured Interstitial Cells of Cajal from Murine Small Intestine.
- Author:
Seok CHOI
1
;
Kyung Won CHO
;
Jong Hyun REU
;
Jun Soo KIM
;
Hyun Sik MUN
;
Myung Young KIM
;
Kwang Chul PARK
;
Gwang Sik HEO
;
Sung Jong CHANG
;
Cheol Ho YEUM
;
Pyung Jin YOON
;
Jae Yeoul JUN
Author Information
1. Department of Physiology, College of Medicine, Chosun University, Gwangju, Korea. jyjun@chosun.ac.kr
- Publication Type:Original Article
- Keywords:
Prostaglandin E2;
Interstitial cells of Cajal (ICCs);
Pacemaker currents;
EP2 receptor
- MeSH:
Adenylyl Cyclases;
Dinoprostone*;
Gastrointestinal Tract;
Guanylate Cyclase;
Interstitial Cells of Cajal*;
Intestine, Small*;
Membranes;
Muscles;
Neurotransmitter Agents;
Patch-Clamp Techniques;
Periodicity;
Prostaglandins
- From:The Korean Journal of Physiology and Pharmacology
2004;8(3):153-159
- CountryRepublic of Korea
- Language:English
-
Abstract:
The interstitial cells of Cajal (ICCs) are the pacemaker cells in gastrointestinal tract and generate electrical rhythmicity in gastrointestinal muscles. Therefore, ICC may be modulated by endogenous agents such as neurotransmitter, hormones, and prostaglandins (PGs). In the present study, we investigated the effects of prostaglandins, especially PGE2, on pacemaker currents in cultured ICCs from murine small intestine by using whole-cell patch clamp techniques. ICCs generated spontaneous slow waves under voltage-clamp conditions and showed a mean amplitude of -452+/-39 pA and frequency of 18+/-2 cycles/min (n=6). Treatments of the cells with PGE2 (1muM) decreased both the frequency and amplitude of the pacemaker currents and increased the resting currents in the outward direction. PGE2 had only inhibitory effects on pacemaker currents and this inhibitory effect was dose-dependent. For characterization of specific membrane EP receptor subtypes, involved in the effects of PGE2 on pacemaker currents in ICCs, EP receptor agonists were used: Butaprost (1muM), EP2 receptor agonist, reduced the spontaneous inward current frequency and amplitude in cultured ICCs (n=5). However sulprostone (1muM), a mixed EP1 and EP3 agonist, had no effects on the frequency, amplitude and resting currents of pacemaker currents (n=5). SQ-22536 (an inhibitor of adenylate cyclase; 100muM) and ODQ (an inhibitor of guanylate cyclase; 100muM) had no effects on PGE2 actions of pacemaker currents. These observations indicate that PGE2 alter directly the pacemaker currents in ICCs, and that the PGE2 receptor subtypes involved are the EP2 receptor, independent of cyclic AMP- and GMP-dependent pathway.
