A Novel Pathway Underlying the Inhibitory Effects of Melatonin on Isolated Rat Urinary Bladder Contraction.
10.4196/kjpp.2012.16.1.37
- Author:
June Hyun HAN
1
;
In Ho CHANG
;
Soon Chul MYUNG
;
Moo Yeol LEE
;
Won Yong KIM
;
Seo Yeon LEE
;
Shin Young LEE
;
Seung Wook LEE
;
Kyung Do KIM
Author Information
1. Department of Urology, KEPCO Medical Foundation, Han-il General Hospital, Seoul 132-703, Korea.
- Publication Type:Original Article
- Keywords:
Melatonin;
Urinary bladder;
Smooth muscles;
Overactive bladder;
Nocturia
- MeSH:
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester;
4-Aminopyridine;
Acetylcholine;
Animals;
Benzylamines;
Bethanechol;
Calcium Channels;
Contracts;
Melatonin;
Muscle, Smooth;
Muscles;
Nocturia;
Phenylephrine;
Phosphotransferases;
Potassium Channel Blockers;
Quaternary Ammonium Compounds;
Rats;
Rats, Sprague-Dawley;
Relaxation;
Sulfonamides;
Urinary Bladder;
Urinary Bladder, Overactive;
Verapamil
- From:The Korean Journal of Physiology and Pharmacology
2012;16(1):37-42
- CountryRepublic of Korea
- Language:English
-
Abstract:
The aim of the present study was to elucidate the direct effects of melatonin on bladder activity and to determine the mechanisms responsible for the detrusor activity of melatonin in the isolated rat bladder. We evaluated the effects of melatonin on the contractions induced by phenylephrine (PE), acetylcholine (ACh), bethanechol (BCh), KCl, and electrical field stimulation (EFS) in 20 detrusor smooth muscle samples from Sprague-Dawley rats. To determine the mechanisms underlying the inhibitory responses to melatonin, melatonin-pretreated muscle strips were exposed to a calcium channel antagonist (verapamil), three potassium channel blockers [tetraethyl ammonium (TEA), 4-aminopyridine (4-AP), and glibenclamide], a direct voltage-dependent calcium channel opener (Bay K 8644), and a specific calcium/calmodulin-dependent kinase II (CaMKII) inhibitor (KN-93). Melatonin pretreatment (10(-8)~10(-6) M) decreased the contractile responses induced by PE (10(-9)~10(-4) M) and Ach (10(-9)~10(-4) M) in a dose-dependent manner. Melatonin (10(-7) M) also blocked contraction induced by high KCl ([KCl]ECF; 35 mM, 70 mM, 105 mM, and 140 mM) and EFS. Melatonin (10(-7) M) potentiated the relaxation response of the strips by verapamil, but other potassium channel blockers did not change melatonin activity. Melatonin pretreatment significantly decreased contractile responses induced by Bay K 8644 (10(-11)~10(-7) M). KN-93 enhanced melatonin-induced relaxation. The present results suggest that melatonin can inhibit bladder smooth muscle contraction through a voltage-dependent, calcium-antagonistic mechanism and through the inhibition of the calmodulin/CaMKII system.
