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.

SUMMARY. Adrenomedullin (AM) is a biologically active peptide recently isolated from phaeochromocytoma. We report here the distribution and characterization of immunoreactive AM and gene expression of AM in human gastrointestinal tissue. Using a sensitive radioimmunoassay system for the peptide, immunoreactive human AM was detected in the stomach, duodenum, jejunum, ileum and colon. The AM concentration of these tissues was about 0-4'--~'8 prnol/g wet tissue. Reverse phase and gel filtration high-performance liquid chromatographies showed that most of the immunoreactive AM in stomach and jejunum was identical to authentic human AM. By northern blot analysis, human AM mRNA was found to be expressed ubiquitously in the human gastrointestinal tissues. Furthermore, an immunohistochemical study revealed that immunoreactive AM cells were present in the gastrointestinal glands. These results suggest that AM may play some role as a gastrointestinal hormone. Additional key phrases: radioimmunoassay; mRNA; immunohistochemistry; calcitonin-gene-related peptide; vasorelaxantAdrenomedullin (AM) is a potent vasorelaxing and hypotensive peptide isolated from human phaeochromocytoma by monitoring the activity of elevating rat platelet cyclic adenosine monophosphate (cAMP).! AM has a slight homology with calcitonin-gene-related peptide (CG RP).1 Since the vasodilating activity of AM is the same as that of CGRP, which is one of the strongest vasorelaxants,' AM and CGRP are assumed to belong to the same superfamily. A cDNA clone encoding a human AM precursor was isolated from the human phaeochromocytoma eDNA library and its complete nucleotide sequence was determined." The precursor for the human AM (preproAM) is 185 amino acids in length, including the AM sequence. ' We have reported the distribution of irnmunoreactive (ir)-AM and the gene expression of AM in human tissues.i-' AM was found to be widely biosynthesized, in the cardiovascular system among others. Gene expression of AM was observed in rat small intestine," and AM increased blood flow of the stomach and small Correspondence: Tanenao Eta MD. intestine in spontaneously hypertensive rats." However, precise localization of ir-AM and gene expression of AM in human gastrointestinal (GI) tissues has never been reported. In the present study, in order to elucidate the physiological role of AM in the human GI tract, we have investigated the distribution and gene expression of AM in the human GI tissues using radioimmunoassay (RIA), northern blot analysis and immunohistochemical analysis. MATERIALS AND METHODSRIA for human AM RIA for human AM was carried out by the previously described method" using an antiserum (# I 72CI -7) against human AM[40-52]NH 2 .3 The incubation buffer for the RIA was 50 mmol/L sodium phosphate buffer (pH 7,4) containing bovine serum albumin (BSA) treated with 0·5% N-ethyl-maleimide, 0·05% Triton X-IOO, 80 mmol/L sodium chloride, 25 mmol/L EDTA (sodium salt) and 0·05% sodium azide. One hundred fLL of standard (human AM) or unknown sample was incubate...

Among older hypertensive patients with antihypertensive medications, those who had echocardiographically determined cardiac hypertrophy may be at high risk for cognitive dysfunction, irrespective of their office BP and 24-h BP levels.

A 19-year-old man with severe active ulcerative colitis was admitted to our hospital where he was prescribed 80 mg prednisolone and underwent leukocytapheresis (LCAP). Two weeks after initiating therapy, his symptoms had not recovered. We administered cyclosporin via continuous intravenous infusion for 12 days. Although his clinical symptoms improved, he complained of severe headache. Immediate plain computed tomography (CT) and magnetic resonance imaging angiography (MRA) revealed extensive thrombosis in the superior sagittal sinus and right transverse sinus. We treated this condition with the anticoagulant agent, heparin, which prevents and can treat venous thrombosis. We report an occurrence of cerebral sinus thrombosis accompanying ulcerative colitis, where active anticoagulant therapy was useful.

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