title: Mechanism of bombesin-induced tonic contraction of the porcine lower esophageal sphincter.
abstract: Gastroesophageal reflux disease (GERD) is a disorder that is related to an incompetent lower esophageal sphincter (LES). Previous studies showed that bombesin could increase LES pressure in humans and opossums. The aim of the present study was to characterize the effects of bombesin on porcine LES contraction. We used the selective agonists, neuromedin B (NMB), gastrin-releasing peptide (GRP), and [D-Tyr(6),Apa-4Cl(11),Phe(13),Nle(14)]bombesin-(6-14) (DTACPN-BN), as well as receptor antagonists of bombesin receptor subtype 2 (BB2), and 3 (BB3) for ex vivo contraction studies. Atropine, nifedipine, tetrodotoxin, and ω-conotoxin GVIA were used to explore the agonist-induced LES contraction mechanism. Reverse transcription polymerase chain reaction and immunohistochemistry were applied to detect bombesin receptor expression. Our results indicate that GRP and DTACPN-BN, but not NMB, induced tonic contractions of the porcine LES in a dose-dependent manner, and the contractions were inhibited with selective BB2 and BB3 antagonists. The GRP-induced contraction is mainly caused by L-type Ca(2+) channel-mediated Ca(2+) influx. However, DTACPN-BN-induced contractions are associated with neuronal conduction. RT-PCR and immunohistochemistry revealed that BB2 and BB3 were expressed in the porcine LES. Bombesin-induced tonic contraction of the LES is mediated through BB2 and BB3. Bombesin, BB2, and BB3 agonists might have the potential to treat GERD.
authors.affiliation: School of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan, No. 100, Shih-Chuan 1st Road, Sanmin District, Kaohsiung City, Taiwan, R.O.C.|Department of Pediatrics, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan, No. 1, Yi-Da Road, Yan-Chao, Kaohsiung City, Taiwan, R.O.C.
authors.forename: Ching-Chung
authors.initials: CC
authors.lastname: Tsai
authors.affiliation: Department of Occupational Therapy, I-Shou University, Kaohsiung, Taiwan, No. 8, Yi-Da Road, Yan-Chao, Kaohsiung City, Taiwan, R.O.C.|Department of Pharmacy, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan, No. 1, Yi-Da Road, Yan-Chao, Kaohsiung City, Taiwan, R.O.C.
authors.forename: Li-Ching
authors.initials: LC
authors.lastname: Chang
authors.affiliation: Department of Pathology, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan, No. 1, Yi-Da Road, Yan-Chao, Kaohsiung City, Taiwan, R.O.C.
authors.forename: Kai-Jen
authors.initials: KJ
authors.lastname: Lin
authors.affiliation: Department of Pediatrics, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan, No. 1, Yi-Da Road, Yan-Chao, Kaohsiung City, Taiwan, R.O.C.
authors.forename: Shu-Leei
authors.initials: SL
authors.lastname: Tey
authors.affiliation: Department of Pediatrics, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan, No. 1, Yi-Da Road, Yan-Chao, Kaohsiung City, Taiwan, R.O.C.
authors.forename: Yu-Tsun
authors.initials: YT
authors.lastname: Su
authors.affiliation: School of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan, No. 100, Shih-Chuan 1st Road, Sanmin District, Kaohsiung City, Taiwan, R.O.C.
authors.forename: Ching-Wen
authors.initials: CW
authors.lastname: Liu
authors.affiliation: School of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan, No. 100, Shih-Chuan 1st Road, Sanmin District, Kaohsiung City, Taiwan, R.O.C.
authors.forename: Tong-Rong
authors.initials: TR
authors.lastname: Tsai
authors.affiliation: Department of Internal Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan, No. 1, Yi-Da Road, Yan-Chao, Kaohsiung City, Taiwan, R.O.C.|School of Medicine, I-Shou University, Kaohsiung, Taiwan, No. 8, Yi-Da Road, Yanchao, Kaohsiung City, Taiwan, R.O.C.
authors.forename: Shih-Che
authors.initials: SC
authors.lastname: Huang
mesh_terms: D000818:Animals; D001839:Bombesin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000378:metabolism; D049630:Esophageal Sphincter, Lower / Q000187:drug effects* / Q000378:metabolism*; D019886:Gastrin-Releasing Peptide / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D015287:Neurokinin B / Q000031:analogs & derivatives / Q000494:pharmacology; D018004:Receptors, Bombesin / Q000378:metabolism; D013552:Swine
chemical_list: D020746:Calcium Channels, L-Type; D018004:Receptors, Bombesin; D019886:Gastrin-Releasing Peptide; D015287:Neurokinin B; C038393:neuromedin B; D001839:Bombesin; D002118:Calcium