Effect of adrenomedullin on ion transport and muscle contraction in rat distal colon

Fukuda, Kazuhito; Tsukada, Hideaki; Onomura, M.; Saitō, Tsunemasa; Kodama, Mitsuo; Nakamura, Hiroshi; Taniguchi, Takao; Tominaga, Mitsuhiro; Hosokawa, Munetaka; Seino, Yutaka

doi:10.1016/s0196-9781(98)00043-6

Cited by 18 publications

(18 citation statements)

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“…5B) imply that the relaxation may be mediated through the activation of ␤ 3 -AR. Since AM was suggested to release catecholamines from chromaffin and nervous cells (Nussdorfer et al, 1997;Fukuda et al, 1998), it is possible the indirect contribution of ␤-AR agonists to the AM induced relaxation. To prevent this pathway, all experiments were performed in the present of TTX.…”

Section: Discussionmentioning

confidence: 99%

“…However, in contrast to vascular muscles, the contribution of AM to the regulation of contractile responses of the visceral muscles have not been much investigated. Only a single report indicates that AM is able to modify ion transport and inhibit muscle contraction in the rat colon (Fukuda et al, 1998). To obtain further information about the role of AM in the gut, the contents of preproadrenomedullin mRNA, the level of AM, and the effects of AM on the rat ileum precontracted with a natural regulator of smooth muscle tone, serotonin, have been studied.…”

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confidence: 99%

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The Inhibitory Effect of Adrenomedullin in the Rat Ileum: Cross-Talk with β₃-Adrenoceptor in the Serotonin-Induced Muscle Contraction

Kravtsov

Hwang²,

Tang³

2003

J Pharmacol Exp Ther

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In contrast to vascular muscles, the contribution of a hypotensive peptide adrenomedullin (AM) to the regulation of visceral smooth muscles is obscure. The content, synthesis, and effects of AM on the muscular tone in rat ileum were explored. It was found that there was immunoreactive AM (301 pg/mg of protein) and AM mRNA expression (162 fg/pg actin mRNA) in the ileum and that AM evoked relaxation in ileal strips (K i ϭ 0.85 nM) precontracted with serotonin. Antagonists of both AM (AM ) and calcitonin gene-related peptide ) receptors did not affect this AM-induced relaxation, whereas it was suppressed by a selective blocker of ␤ 3 -adrenoreceptor (SR 59230A). The AM-induced relaxation was accompanied by a production of cAMP. Antagonists of protein kinases A (KT 5720 and H-7) and an inhibitor of the ATP-dependent K ϩ -channels (glibenclamide) attenuated the effect of AM. We suggest that AM is a local regulator of the ileal tone, with an inhibitory action on muscle contraction. AM may activate the ␤ 3 -adrenoceptors, resulting in protein kinase A activation, which in turn opens the ATP-dependent K ϩ -channels.The hypotensive peptide, adrenomedullin (AM), was originally purified from both adrenal medulla and pheochromocytoma Kitamura and Eto, 1997;Jougasaki and Burnett, 2000). Two unique structures, a 6-amino acid ring with a disulfide bond and a C-terminal amide in the molecule of AM Hinson et al., 2000;Jougasaki and Burnett, 2000), are likely to determine its vasorelaxation properties. AM shares structural homology with the calcitonin gene-related peptide (CGRP), indicating that AM probably belongs to the CGRP superfamily (Kitamura and Eto, 1997;Hinson et al., 2000;Poyner et al., 2002). The signal transduction pathways have been studied in the greatest detail in the vasculature. A large body of experimental data shows AM synthesis in smooth muscle cells (Kitamura and Eto, 1997;Nishimura et al., 1997) and suggests that AM-induced vasodilation may be mediated by a specific receptor functionally coupled to adenylate cyclase (Eguchi et al., 1994a;Kitamura and Eto, 1997;Nussdorfer et al., 1997;Jougasaki and Burnett, 2000;Poyner et al., 2002). AM-specific receptors are not only found in smooth muscle cells, but also in endothelium cells (Kamitani et al., 1999). It has been reported that the binding of AM to the endothelial receptor can trigger the nitric oxide (NO)-cGMP pathway (Ikeda et al., 1996). Therefore, it is now widely accepted that at least two mechanisms appear to underlie the AM-induced relaxation in vascular muscles: 1) a direct action on vascular smooth muscle cells to increase cAMP (Eguchi et al., 1994a,b;Shimekake et al., 1995;Kitamura and Eto, 1997;Yoshimoto et al., 1998) and 2) an indirect action on endothelial cells to stimulate NO synthesis (Shimekake et al., 1995;Hinson et al., 2000;Jougasaki and Burnett, 2000).The results of mRNA blot analysis reported 10 years ago (Sakata et al., 1993) and later confirmed (Nishimura et al., 1997;Cameron and Fleming, 1998;Sakata et al., 1998) imply that r...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

The Inhibitory Effect of Adrenomedullin in the Rat Ileum: Cross-Talk with β₃-Adrenoceptor in the Serotonin-Induced Muscle Contraction

Kravtsov

Hwang²,

Tang³

2003

J Pharmacol Exp Ther

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“…The density of the cells increases distally in the gut. In the distal colon, AM can also be detected in smooth muscle cells [131]. However, in the porcine gastrointestinal tract, immunoreactive AM and PAMP are more abundant in the small intestine and decrease in the large intestine [137].…”

Section: Adrenomedullin Distribution In the Gastrointestinal Tractmentioning

confidence: 99%

Adrenomedullin regulates intestinal physiology and pathophysiology

Martínez-Herrero

Martı́nez

2016

Domestic Animal Endocrinology

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“…Only a few in vitro reports indicate that AM is able to inhibit muscle contraction in the rat colon and ileum. 14,15 The present study was carried out (i) to evaluate the effects of AM on the intestinal motor profile in fasted Background. Adrenomedullin is a vasodilator peptide that displays a variety of effects, such as hypotension and vasodilatation.…”

Section: Introductionmentioning

confidence: 99%

Possible involvement of adrenomedullin in lipopolysaccharide-induced small-intestinal motility changes in conscious rats

et al. 2005

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Effect of adrenomedullin on ion transport and muscle contraction in rat distal colon

Cited by 18 publications

References 15 publications

The Inhibitory Effect of Adrenomedullin in the Rat Ileum: Cross-Talk with β₃-Adrenoceptor in the Serotonin-Induced Muscle Contraction

The Inhibitory Effect of Adrenomedullin in the Rat Ileum: Cross-Talk with β₃-Adrenoceptor in the Serotonin-Induced Muscle Contraction

Adrenomedullin regulates intestinal physiology and pathophysiology

Possible involvement of adrenomedullin in lipopolysaccharide-induced small-intestinal motility changes in conscious rats

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Effect of adrenomedullin on ion transport and muscle contraction in rat distal colon

Cited by 18 publications

References 15 publications

The Inhibitory Effect of Adrenomedullin in the Rat Ileum: Cross-Talk with β3-Adrenoceptor in the Serotonin-Induced Muscle Contraction

The Inhibitory Effect of Adrenomedullin in the Rat Ileum: Cross-Talk with β3-Adrenoceptor in the Serotonin-Induced Muscle Contraction

Adrenomedullin regulates intestinal physiology and pathophysiology

Possible involvement of adrenomedullin in lipopolysaccharide-induced small-intestinal motility changes in conscious rats

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The Inhibitory Effect of Adrenomedullin in the Rat Ileum: Cross-Talk with β₃-Adrenoceptor in the Serotonin-Induced Muscle Contraction

The Inhibitory Effect of Adrenomedullin in the Rat Ileum: Cross-Talk with β₃-Adrenoceptor in the Serotonin-Induced Muscle Contraction