Functional effects of β3-adrenoceptor on pacemaker activity in interstitial cells of Cajal from the mouse colon.
We investigated the presence of β3-adrenoceptor and its functional effects on pacemaker potentials in colonic interstitial cells of Cajal (ICCs) from mice. The whole-cell patch clamp technique was used to record pacemaker potentials in cultured ICCs and reverse transcription polymerase chain reaction (RT-PCR) was performed to detect the mRNA transcript levels β-adrenoceptors. The β3-adrenoceptor agonist, BRL37344, reduced the frequency of pacemaker potentials in a concentration-dependent manner. The inhibitory effects of BRL37344 were blocked by the pretreatment of propranolol, a nonspecific β-adrenoceptor antagonist, but not by the selective β1-adrenoceptor antagonist atenolol and the selective β2-adrenoceptor antagonist butoxamine. β3-adrenoceptor antagonists SR59230A and L748337 blocked the inhibitory effects of BRL37344. RT-PCR revealed mRNA transcripts of β1- and β3-adrenoceptor, but not β2-adrenoceptor, in c-kit- and Ano-1-positive colonic ICCs. The K(+) channel blockers tetraethylammonium, apamin, and glibenclamide did not block the effects of BRL37344. N(ω)-Nitro-l-arginine methyl ester hydrochloride (L-NAME), an NO synthase inhibitor, and chelerythrine, a protein kinase C inhibitor, also did not block the effects of BRL37344. Noradrenaline mimicked the effects of BRL37344 in colonic ICCs. However, the inhibitory effects of noradrenaline on pacemaker potentials were blocked only by pretreatment with atenolol but not by butoxamine, SR59230A, or L748337. In small intestinal ICCs, BRL37344 had no effect on pacemaker potentials and mRNA transcripts of β1-and β2-adrenoceptor, but not β3-adrenoceptor were detected. These results suggest that β3-adrenoceptors are present in colonic ICCs and may play a role in regulating gastrointestinal motility by the inhibition of pacemaker potentials.
Department of Physiology, Chonnam National University Medical School, Gwangju 501-757, Republic of Korea.
Mei Jin
MJ
Wu
Division of Natural Medical Science, College of Health Science, Chosun University, Gwangju 501-759, Republic of Korea.
Dong Hoon
DH
Shin
Department of Internal Medicine, College of Medicine, Chosun University, Gwangju 501-759, Republic of Korea.
Man Yoo
MY
Kim
Department of Internal Medicine, College of Medicine, Chosun University, Gwangju 501-759, Republic of Korea.
Chan Guk
CG
Park
Department of Internal Medicine, College of Medicine, Chosun University, Gwangju 501-759, Republic of Korea.
Young Dae
YD
Kim
Department of Internal Medicine, College of Medicine, Chosun University, Gwangju 501-759, Republic of Korea.
Jun
J
Lee
Department of Internal Medicine, College of Medicine, Chosun University, Gwangju 501-759, Republic of Korea.
Il Koo
IK
Park
Department of Physiology, College of Medicine, Chosun University, Gwangju 501-759, Republic of Korea.
Seok
S
Choi
Department of Physiology and Biophysics, College of Medicine, Seoul National University, Seoul 110-799, Republic of Korea.
Insuk
I
So
Department of Physiology, Chonnam National University Medical School, Gwangju 501-757, Republic of Korea. Electronic address: parkjs@jnu.ac.kr.
Jong Seong
JS
Park
Department of Physiology, College of Medicine, Chosun University, Gwangju 501-759, Republic of Korea. Electronic address: jyjun@chosun.ac.kr.
Jae Yeoul
JY
Jun
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000627:Aminophenols / Q000494:pharmacology; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D053119:Benzophenanthridines / Q000494:pharmacology; D001683:Biological Clocks / Q000187:drug effects / Q000502:physiology*; D002078:Butoxamine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D003106:Colon / Q000166:cytology* / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004983:Ethanolamines / Q000037:antagonists & inhibitors / Q000494:pharmacology; D005260:Female; D056885:Interstitial Cells of Cajal / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D022702:Receptors, Adrenergic, beta-3 / Q000096:biosynthesis / Q000502:physiology*; D013449:Sulfonamides / Q000494:pharmacology
C097869:3-(2-ethylphenoxy)-1-(1,2,3,4-tetrahydronaphth-1-ylamino)-2-propanol oxalate; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D000627:Aminophenols; D053119:Benzophenanthridines; D004983:Ethanolamines; C120576:L 748,337; D026902:Potassium Channel Blockers; D011412:Propanolamines; D022702:Receptors, Adrenergic, beta-3; D013449:Sulfonamides; D002078:Butoxamine; D001262:Atenolol; C057368:BRL 37344; D011433:Propranolol; C016299:chelerythrine; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine
Colon.; Interstitial cells of Cajal; Pacemaker potentials; β(3)-adrenoceptor