Tsutomu Chiba

Human α-calcitonin gene-related peptide-(8-37) as an antagonist of exogenous and endogenous calcitonin gene-related peptide

Abstract The C-terminal fragment of the human α-calcitonin gene-related peptide (hCGRP), hCGRP-(8–37) competitively antagonized both the positive inotropic effect of hCGRP in the guinea-pig isolated left atria (pA2 6.89) and the smooth muscle relaxant effect of hCGRP in the rat isolated vas deferens (pA2) but left the response to isoprenaline unaffected in both preparations. In addition, hCGRP-(8–37) reduced the responses produced by activation of the ‘efferent’ function of capsaicin-sensitive primary afferents in both preparations thus providing pharmacological evidence for the involvement of endogenous CGRP. hCGRP-(8–37) appears a useful tool to establish the physiological role of CGRP in peripheral preparations from different species.

Receptors for gastrin on gastric carcinoid tumor membrane of Mastomys natalensis

Specific binding sites for human gastrin I (gastrin) were identified in a crude membrane preparation from the gastric carcinoid tumor of Mastomys (Praomys) natalensis. The binding of 125I-gastrin to the carcinoid tumor membrane was saturable, and Scatchard analysis of the data revealed a single class of binding site with a dissociation constant of 139.2 pM and a maximal binding capacity of 23.5 fmol/mg protein. Gastrin and CCK8 equipotently and dose-dependently displaced the binding of 125I-gastrin to the membrane. GTP but not ATP decreased 125I-gastrin binding to the membrane, and removal of Mg2+ attenuated this inhibitory action of GTP. The GTP-induced reduction of 125I-gastrin binding was found to be due to a decrease in binding affinity without a change in binding capacity. These results clearly indicate the presence of specific binding sites for gastrin, probably coupled to guanine nucleotide-binding protein, in the carcinoid tumor membrane of Mastomys, and suggest that gastrin has possible biological actions on these tumors.

Two cases of gastric antral vascular ectasia-Response to medical treatment

SummaryTwo patients with severe iron deficiency anemia and gastric antral vascular ectasia (GAVE) are reported. The anemia caused by the chronic blood loss from the abnormally dilated mucosal and submucosal capillary veins in the gastric antrum was unresponsive to oral iron supplementation. However, one of the patients was successfully treated with intramuscular injection of (Asu17) eel calcitonin. The other one was treated by oral prednisolone with resulting improvement iron deficiency anemia. The possible mechanisms of successful calcitonin and prednisolone treatments on chronic blood loss from GAVE is discussed.

Cellular mechanisms of somatostatin action in the gut

We have used isolated canine parietal cells to examine the receptor and postreceptor events mediating the inhibitory effects of somatostatin on acid secretion. Somatostatin-14 (S14) and somatostatin-28 (S28) dose dependently inhibited parietal cells stimulated by secretagogues that activate both the adenylate cyclase/cyclic adenosine monophosphate and the inositol phospholipid/protein kinase C cascades. The inhibitory action was mediated via a specific cell surface receptor that consists of a single subunit protein (molecular weight 99,000 d). This receptor recognized S14 and S28 equally well. Somatostatin inhibited parietal cell activity via mechanisms that are both dependent on and independent of a pertussis toxin-sensitive inhibitory guanine nucleotide binding protein.

Calcitonin inhibits the growth of human gastric carcinoma cell line KATO III

Calcitonin has a wide variety of actions on gastrointestinal function. In this study, we investigated the effects of calcitonin on the growth of human gastric carcinoma cell line KATO III in comparison with those of calcitonin gene-related peptide (CGRP). Calcitonin, but not CGRP, significantly and dose-dependently inhibited the growth of KATO III cells. This inhibition of cell growth was accompanied by an increase in cyclic AMP production. The proliferation of KATO III cells was also inhibited by forskolin and dibutyryl cyclic AMP, although agents which do not stimulate cyclic AMP production had no effect. Furthermore, in the presence of GTP, calcitonin stimulated adenylate cyclase activity in KATO III cell membranes, and this increase was reduced in the absence of GTP. On the other had, neither calcitonin nor CGRP enhanced the turnover of inositolphospholipid or the intracellular Ca2+ level. In addition, 125I-labeled human calcitonin was specifically bound to KATO III cell membranes, and this binding was dose-dependently displaced by unlabeled calcitonin but not CGRP. Furthermore, the specific binding of 125I-labeled human calcitonin to KATO III cell membranes was significantly reduced by addition of GTP but not ATP. These results suggest that calcitonin inhibits the growth of human gastric carcinoma cell line KATO III by stimulating cyclic AMP production via a GTP-dependent process coupled to specific calcitonin receptors.