In tumor cells that coexpress Cx43 and Cx26, the assembly of Cx43 is selectively impaired due to endocytosis. Assembly can be restored upon expressing a Cx43 sorting-motif mutant and mutants that cannot be phosphorylated on Ser-279 or Ser-282.

Heimann. Effects of amylin-related peptides on food intake, meal patterns, and gastric emptying in rats. Am J Physiol Regulatory Integrative Comp Physiol 282: R1395-R1404, 2002. First published January 17, 2002 10.1152/ajpregu.00597. 2001.-We previously demonstrated that amylin inhibits food intake and gastric emptying in rats with half-maximal effective doses (ED 50s) of 8 and 3 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 and maximal inhibitions of 78 and 60%, respectively. In this study of identical design, rats received intravenous infusions of salmon calcitonin (sCT), rat calcitonin (rCT), rat calcitonin gene-related peptide (rCGRP), and rat adrenomedullin (rADM) for 3 h at dark onset, and food intake was measured for 17 h or for 15 min and gastric emptying of saline was measured during the final 5 min. sCT, rCGRP, and rADM inhibited food intake with estimated ED50s of 0.5, 26, and 35 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 and maximal inhibitions of 88, 90, and 49%, respectively. rCT was not effective at doses up to 100 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 . sCT, rCGRP, rADM, and rCT inhibited gastric emptying with ED50s of 1, 130, 160, and 730 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 and maximal inhibitions of 60, 66, 60, and 33%, respectively. These results suggest that amylin and sCT may act by a common mechanism to decrease food intake, which includes inhibition of gastric emptying.calcitonin; calcitonin gene-related peptide; adrenomedullin; anorexia; potency AMYLIN (ALSO CALLED ISLET amyloid polypeptide) is a 37-amino acid peptide that is cosecreted with insulin from the pancreas in response to a meal (11, 51). Amylin has also been detected in gut endocrine cells (35), visceral sensory neurons (36), and throughout the brain (44). Exogenous amylin potently reduces food intake (1, 3, 39), body weight (1), adiposity (41), gastric emptying (10, 39), and gastric acid secretion (15) when administered systemically or into the brain. We recently demonstrated that the minimal effective intravenous dose for amylin-induced inhibition of food intake and gastric emptying in rats (1 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 ) increases plasma amylin by an amount comparable to that produced by a meal (3,39). We also demonstrated that in suppressing feeding and gastric emptying, amylin is at least as potent and efficacious as CCK (39), a physiological inhibitor of food intake and gastric emptying.These results support the hypothesis that amylin acts as a hormonal signal to the brain to inhibit gastric emptying and food intake and that amylin produces satiety, in part, through inhibition of gastric emptying.Calcitonin gene-related peptide (CGRP), calcitonin (CT), and adrenomedullin (ADM), together with amylin, form a family of structurally related peptides with overlapping biological actions (Fig. 1). Each of these peptides inhibits food intake (13,22,32,45) and gastric emptying (8,20,30,38) when administered systemically or into the brain. The teleost peptide salmon CT (sCT) appears to be significantly more potent than either amylin (29) or mammalian CTs (8, 29, 47) in decreasing food intake and gastric emp...

A cholecystokinin receptor (CCKAR) antagonists differing in blood-brain barrier permeability were used to test the hypothesis that duodenal delivery of protein, carbohydrate, and fat produces satiety in part by an essential CCK action at CCKARs located peripheral to the blood-brain barrier. Fasted rats with open gastric fistulas received devazepide (1 mg/kg iv) or A-70104 (700 nmol ⅐ kg Ϫ1 ⅐ h Ϫ1 iv) and either a 30-min intravenous infusion of CCK-8 (10 nmol ⅐ kg Ϫ1 ⅐ h Ϫ1 ) or duodenal infusion of peptone, maltose, or Intralipid beginning 10 min before 30-min access to 15% sucrose. Devazepide penetrates the blood-brain barrier; A-70104, the dicyclohexylammonium salt of N␣-3-quinolinoyl-D-Glu-N,N-dipentylamide, does not. CCK-8 inhibited sham feeding by ϳ50%, and both A-70104 and devazepide abolished this response. Duodenal infusion of each of the macronutrients dose dependently inhibited sham feeding. A-70104 and devazepide attenuated inhibitory responses to each macronutrient. Thus endogenous CCK appears to act in part at CCKARs peripheral to the blood-brain barrier to inhibit food intake. receptor antagonist; devazepide; A-70104; satiety CCK is a peptide that is found throughout the brain and in neurons and endocrine cells of the gastrointestinal tract. Studies demonstrating that type A CCK receptor (CCKAR) antagonists stimulate food intake in a variety of species provide compelling evidence that CCK plays an essential role in producing the satiation that occurs with ingestion of a meal (6,13,14,23,39,48). The popular hypothesis is that CCK, secreted from enteroendocrine cells in the upper small intestine in response to duodenal delivery of nutrients, acts through paracrine stimulation of intestinal vagal sensory neurons to inhibit food intake. This hypothesis is supported by studies demonstrating the existence of CCK-secreting endocrine cells in the epithelium of the upper small intestine (7, 60), CCKARs within vagal afferent nerves (40, 66), activation of intestinal vagal afferent neurons by exogenous and endogenous CCK (17,20,31), and similar attenuation by CCKAR antagonists and vagal neural lesions of anorexic responses to exogenous CCK and nutrient administration (51).Several lines of evidence suggest that this mechanism is not the only one by which CCK produces satiety. For example, we and others have demonstrated that systemic administration of the CCKAR antagonist devazepide can increase food intake in rats whether or not they are vagotomized (45) or pretreated with capsaicin to lesion visceral sensory nerves (52). CCKAR antagonists reported not to cross the bloodbrain barrier [2-naphthalenesulfonyl-L-aspartyl-2-(phenethyl)-amide (25) and A-70104 (64)] have also been reported to have no effect on food intake in rats (22) or pigs (4, 24) when administered systemically under the same conditions in which devazepide stimulates food intake (22, 23). Because CCK does not readily penetrate the blood-brain barrier (41), these results suggest that endogenous CCK may also be acting as a neurotransmitter or neuro...

We report that acetyl-N-Ser-Asp-Lys-Pro (AcSDKP), which removes progenitor cells from cell cycle, in combination with granulocyte-colony stimulating factor (G-CSF) can significantly improve myelorestoration following irradiation (7 Gy). Peripheral blood, spleen and bone marrow (BM) cell recovery and progenitor cell reconstitution [IL-3-responsive colony-forming cells (CFC) and high proliferative potential colony-forming cells (HPP-CFC)] were studied. Studies on the optimal schedule of AcSDKP administration revealed maximal effects on progenitor cells when AcSDKP was administered as a continuous infusion for 3 d starting 24 h prior to irradiation and used in combination with G-CSF. The numbers of CFC and HPP-CFC in the BM were significantly increased following irradiation in mice receiving AcSDKP and G-CSF as compared to either drug alone. The numbers of CFC in the spleen were significantly increased in mice receiving AcSDKP and G-CSF on days 10 and 14 as compared to AcSDKP alone, but not G-CSF. Similarly, CFC and HPP-CFC in the spleen were significantly increased in mice receiving AcSDKP and G-CSF on day 18 as compared to mice receiving PBS and G-CSF. These studies suggest that AcSDKP in combination with G-CSF may have potential for the protection of progenitor cells in patients undergoing intensive chemo- and/or radiotherapy.