Pharmacological characterization of the histamine receptor in the isolated muscularis mucosae of the guinea‐pig oesophagus

Kamikawa

2007

J. Smooth Muscle Res.

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Lamina muscularis mucosae sitting beneath mucosal surface of the digestive tract has received little attention to date compared with external smooth muscle layers. Motor activity of the muscularis mucosae shows a great regional and species difference. Autonomic innervation profile is also different from esophagus to colon or between animal species. Intracellular transduction mechanisms for motor activity of the muscularis mucosae are also different from those of external longitudinal and circular muscles or from vascular and airway smooth muscles. Since the submucosal area is a major source for eicosanoid production, abnormality of muscularis mucosae motor activity may link with abnormality of mucosal absorption and secretion functions. Inflammatory bowel diseases such as diarrhea, irritable bowel syndrome and Crohn's disease accompanied with altered motor activity of the muscularis mucosae. Much attention should be attracted to the human muscularis mucosae as a new therapeutic target for inflammatory bowel diseases.

Section: Responsiveness To Drugsmentioning

confidence: 79%

Muscularis mucosae - the forgotten sibling

Kamikawa

2007

J. Smooth Muscle Res.

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“…The oesophageal muscularis mucosae is innervated chie¯y by excitatory cholinergic nerves and sparsely by inhibitory adrenergic nerves, but not by non-adrenergic and non-cholinergic nerves (Kamikawa & Shimo, 1979;Kamikawa et al, 1982). It is already known that the receptor systems in this tissue for catecholamines, 5-hydroxytryptamine, acetylcholine and histamine are dierent from those in the external smooth muscles (Uchida, 1983;Uchida et al, 1983;Kamikawa et al, 1985;Fujinuma et al, 1985). ET-1 elicits contractions of the isolated oesophageal muscularis mucosae, but the receptor mechanisms and subtypes involved in this eect are still uncharacterized.…”

Section: Introductionmentioning

confidence: 99%

Pharmacological characterization of endothelin‐induced contraction in the guinea‐pig oesophageal muscularis mucosae

Yuzuki

Kamikawa

1998

British J Pharmacology

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1 In the oesophageal muscularis mucosae, we examined the eects of endothelin-1 (ET-1), endothelin-2 (ET-2), endothelin-3 (ET-3) and sarafotoxin S6c (SX6c) as agonists, and FR139317, BQ-123 and RES-701-1 as endothelin receptor antagonists. 2 All of the endothelins produced tonic contractions which were frequently superimposed on rhythmic motility in a concentration-dependent manner. The order of potency (7log EC 50 ) was ET-1 (8.61)=SX6c (8.65)4ET-2 (8.40) ). 3 FR139317 (1 ± 3 mM) and BQ-123 (1 mM) caused parallel rightward shifts of the concentrationresponse curve to ET-1, but at higher concentrations caused no further shift. RES-701-1 (3 mM) caused a rightward shift of the concentration-response curve to ET-1, while RES-701-1 (10 mM) had no additional eect. RES-701-1 (0.1 ± 1 mM) concentration-dependently caused a rightward shift of the concentrationresponse curve to SX6c. The contraction to ET-1 (10 nM) in preparations desensitized to the actions of SX6c was greatly inhibited by pretreatment with FR139317 (10 mM). 4 Modulation of the Ca 2+ concentration in the Krebs solution caused the concentration-response curve to ET-1 or SX6c to shift to the right and downward as external Ca 2+ concentrations decreased. Verapamil (30 mM) abolished rhythmic motility induced by ET-1 or SX6c. Ni 2+ (0.1 mM) weakly inhibited ET-1-or SX6c-induced tonic contraction. SK&F 96365 (60 mM) completely inhibited ET-1-induced contractions. 5 We conclude that there are two types of ET-receptors, excitatory ET A -and ET B -receptors in the oesophageal muscularis mucosae. These receptors mediate tonic contractions predominantly by opening receptor-operated Ca 2+ channels (ROCs) and partly by opening T-type Ca 2+ channels, and mediate rhythmic motility by opening L-type Ca 2+ channels.

“…The receptor-mediated contraction of the esophageal muscularis mucosae presumably links with the receptoractivated Ca 2+ influx pathway [1][2][3][4]. Recently, we have reported that exogenously applied BaCl 2 selectively inhibits the receptor-mediated contraction of the guinea pig esophageal muscularis mucosae [5].…”

Section: Introductionmentioning

confidence: 99%

Effects of Ba<sup>2+</sup> on Norepinephrine-Induced Contraction of Rat Thoracic Aorta in vitro

Saito¹,

Kitajima²,

et al. 2000

Pharmacology

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The aim of this study was to examine the effect of exogenously applied BaCl₂ on the norepinephrine-induced contraction of the rat thoracic aorta. Exogenously applied BaCl₂ (0.3–1 mmol/l) slightly elevated the norepinephrine-induced sustained contraction of the rat thoracic aorta in the absence of nicardipine (1 μmol/l). In the aortic preparation pretreated with nicardipine (1 μmol/l), exogenous BaCl₂ (0.1–3 mmol/l) did not elevate the norepinephrine-induced sustained contraction, but the high concentration of BaCl₂ (10 mmol/l) slightly inhibited the norepinephrine-induced tone. In a Ca²⁺-free Krebs bi- carbonate solution (KBS) containing norepinephrine (1 μmol/l) or a Ca²⁺-free K⁺-rich (60 mmol/l) KBS, exogenously applied BaCl₂ (1–30 mmol/l) caused a sustained contraction of the rat thoracic aorta, and this sustained contraction was completely inhibited by nicardipine (1 μmol/l). Exogenous CaCl₂ (0.1–3 mmol/l) also caused a sustained contraction of the aortic preparation in a Ca²⁺- free KBS containing norephinephrine (1 μmol/l), but such a sustained contraction was partly inhibited by nicardipine (3 μmol/l). These results indicate that Ba²⁺ elevates the norepinephrine-induced tone of the rat isolated thoracic aorta by permeating voltage-dependent Ca²⁺ channels in the absence of nicardipine, but that Ba²⁺ has a minor modification on the norepinephrine-induced sustained contraction of the nicardipine-pretreated preparation.