Adrenomedullin in the gastrointestinal tract. Distribution and gene expression in rat and augmented gastric adrenomedullin after fasting

Abstract

The aim of this study was to investigate the regional distribution, molecular forms, and gene expression of adrenomedullin in the rat gastrointestinal tract and to examine physiological changes in gastric adrenomedullin after 24-h fasting. The tissue concentration was measured by radioimmunoassay. The molecular forms were analyzed by high performance liquid chromatography. mRNA levels were quantified by Northern blotting and cells positive for adrenomedullin immunoreactivity were localized by immunohistochemistry. A high concentration of adrenomedullin was found in stomach, cecum, and colon (450-520 fmol/g wet tissue). Adrenomedullin immunoreactivity was also detected in duodenum, jejunum, and ileum (200-250 fmol/g wet tissue). Transcripts of the adrenomedullin gene were widely expressed throughout the gastrointestinal tract. The major form of adrenomedullin immunoreactivity in stomach and colon corresponded precisely with authentic adrenomedullin peptide. Adrenomedullin immunoreactive cells were present in the gastrointestinal endocrine system. The concentration and mRNA level of gastric adrenomedullin after fasting were significantly increased compared with findings in controls. Adrenomedullin is ubiquitous in the gastrointestinal tract, and may be produced by endocrine cells. The results suggest that adrenomedullin, through its potent vasodilating activity, may play some role, in the stomach including the regulation of the mucosal blood flow.

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

“…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 rat AM mRNA can also be expressed in visceral smooth …”

“…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 rat AM mRNA can also be expressed in visceral smooth muscle cells of the gastrointestinal tract. Immunoreactive AM (ir-AM) was detected in different regions of the gastrointestinal system: stomach, duodenum, jejunum, ileum, cecum, and colon (Mulder et al, 1996;Sakata et al, 1998;Kiyomizu et al, 2001).…”

“…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 rat AM mRNA can also be expressed in visceral smooth …”

“…Immunoreactive AM (ir-AM) was detected in different regions of the gastrointestinal system: stomach, duodenum, jejunum, ileum, cecum, and colon (Mulder et al, 1996;Sakata et al, 1998;Kiyomizu et al, 2001). 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.…”

Effect of Adrenomedullin Administration in Two Rat Models of Experimental Inflammatory Bowel Disease

“…AM has been shown to be widely distributed in gastrointestinal tissues including the stomach, duodenum, jejunum, ileum, colon, and rectum 16,17 . AM receptor expression has also been shown to be widely distributed in many of these organs and tissues 18,19 .…”