Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies have indicated that intracellular Ca2+ is involved in fetal bovine serum (FBS)- or growth factor (GF)-stimulated Na+ influx in human foreskin fibroblasts (HSWP). In the present study, 45Ca2+ efflux from serum-deprived HSWP cells was measured in response to 10% FBS or GF [lys-bradykinin, vasopressin, epidermal growth factor, and insulin]. Efflux data were analyzed using a computer program and the best fit indicated the presence of three Ca2+ compartments: a compartment (C1) with a very fast turnover rate, one (C2) with a fast turnover rate, and one (C3) with a slow turnover rate. When serum-deprived cells were treated with 10% FBS, efflux from C2 and C3 increased significantly (p less than 0.05). Similar effects on efflux were observed when serum-deprived cells were treated with individual GFs. Combination of the four GFs produced a higher stimulation than any single factor and a response that was equal to that of FBS. On the other hand, when cells were serum-treated in the presence of the intracellular Ca2+ antagonist, B-(N-N,diethylamino)-octyl-3,4,5-trimethoxybenzoate (TMB-8), 45Ca2+ efflux from C2 was substantially reduced. Finally, when cells were treated with the Na+ transport inhibitor amiloride, there was no significant effect on serum-stimulated Ca2+ efflux. These results are consistent with a FBS- or GF-induced mobilization of Ca2+ that can be blocked by intracellular Ca2+ antagonists, and support the hypothesis that the action of these agents on Na+ influx may be via their effects on intracellular Ca2+.
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PMID:Efflux of 45Ca2+ from human fibroblasts in response to serum or growth factors. 661

Endothelins modulate not only vasoregulation but also neurotransmission and hormone secretion, specifically vasopressin (AVP) secretion. The present studies were designed to ascertain the site of action and the participation of membrane cation channels mediating endothelin-3-induced AVP release. Experiments were performed using standard and compartmentalized hypothalamo-neurohypophysial explants. The stimulatory action of endothelin-3 on AVP release occurred at the neural lobe, consistent with the failure of sodium channel blockade to decrease AVP secretion. Calcium channel antagonism or chelation of extracellular calcium inhibited neurohormone release, but blockade of calcium mobilization from intracellular stores with 8-(diethyl-amino)octyl 3,4,5-trimethoxybenzoate hydrochloride (TMB-8) did not. Inhibition of the calcium-activated potassium channel with charybdotoxin increased AVP levels dose dependently. Potassium ionophore abolished this response, as did TMB-8, but inhibition of calcium entry failed to do so. A subthreshold dose of charybdotoxin potentiated AVP secretion to submaximal stimulation with endothelin-3 that was prevented only by concomitant blockade of calcium influx and intracellular mobilization. The data support interaction between calcium and potassium channels at the secretory terminal. Collectively, these data are consistent with endothelin-3 receptor activation at the secretory terminal initiating calcium entry, thereby leading to depolarization independent of sodium conductances. This mechanism is opposed by hyperpolarizing forces linked to calcium accumulation, namely, the charybdotoxin-sensitive calcium-activate potassium channel. Interaction of the depolarizing and repolarizing systems enables grade AVP secretion from the neural lobe. These findings do not preclude the participation of other systems as well.
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PMID:Cation channel mechanisms in ET-3-induced vasopressin secretion by rat hypothalamo-neurohypophysial explants. 753 90

In order to explore the mechanism of action of vanadyl sulfate (VOSO4), previously described as an antidiabetic and antihypertensive agent, we have investigated the role of calcium and tyrosine phosphorylation in the contractile responses of rat aorta or skinned rabbit mesenteric artery rings. VOSO4 induced a concentration-dependent contraction of aorta (pD2 = 3.2), which was potentiated by endothelium removal (pD2 = 4.2). After a first exposure to VOSO4, no change in responsiveness was observed even though high vanadium concentrations had accumulated in the aortic tissue (approximately 4 x 10(-3) M). VOSO4 induced, in calcium-free medium, a significant response that, relative to contractions measured in Krebs-Henseleit buffer, was higher (36%) than norepinephrine (16%)-, arginine-vasopressin (8%)- or KCI (5%)-induced responses. 8-(N,N-diethylamino)octyl 3,4,5-trimethoxybenzoate hydrochloride (TMB-8), an intracellular calcium release inhibitor, did not modify VOSO4-induced response either in the presence or in the absence of ambient calcium. On skinned preparations, VOSO4 antagonized Ca++-induced contraction. The tyrosine kinase inhibitors tyrphostin 23 (T23) and tyrphostin 47 (T47) potentiated by 4- and 14-fold, respectively, the activity of VOSO4, in contrast to the lack of effect of T47 on pervanadate-induced contraction. When phosphotyrosine content was revealed by Western blotting, VOSO4 had no effect alone, but in the presence of T47, it dramatically increased the phosphotyrosine content. This result contrasts again with PV-induced tyrosine phosphorylation, which was blocked by T47. These data suggest that the signaling events involved in vascular effects of VOSO4, although they depend little on calcium mobilization, are related to tyrosine phosphorylation, likewise through a pathway different from that of pervanadate.
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PMID:Characterization of vanadyl sulfate effect on vascular contraction: roles of calcium and tyrosine phosphorylation. 910 36

A specific sugar-modified peptide has previously been shown to have renal targeting potential in vivo and to have a specific binding site which has been identified in the kidney membrane fraction. In this report, we studied the inhibitory effects of glycosylated derivatives on the binding of [3H]Glc-O-C8-AVP [a glucosylated derivative of Arg8-vasopressin (AVP), Kd = 55 nM] to clarify the structural requirements necessary for renal recognition. Glc-S-C7-Me (octyl beta-D-thioglucoside) markedly inhibited the binding, to a much greater extent than Glc-O-C7-Me (octyl beta-D-glucoside) and Gal-S-C7-Me (octyl beta-D-thiogalactoside). Also, [3H]Glc-S-C7-Me was shown to have a specific binding site on the kidney membrane (Kd = 17 nM, Bmax = 24 pmol/mg protein) rather than the liver membrane and, in addition, Glc-S-C7-Me exhibited effective and selective renal uptake in vivo. To examine the possibility that Glc-S-C7-Me might be of practical use as a renal targeting vector, AVP, tryptamine and 4-nitrobenz-2-oxa-1,3-diazole were modified with Glc-S-C8- and the tissue uptake of the resulting derivatives was evaluated. All of these derivatives showed clear renal targeting potential because the apparent uptake clearance by the kidney was greater than 3 ml/min/g kidney in each case. As far as the AVP derivatives were concerned, derivatives having different numbers of methylene groups were compared with Glc-S-C8-AVP. Glc-S-C11-AVP exhibited increased kidney targeting potential, whereas that of Glc-S-C5-AVP was reduced. These differences suggest that the "alkylglycoside" moiety is important for renal uptake. In addition, these renally targeted derivatives inhibited the binding of [3H]Glc-S-C7-Me to the kidney membrane fraction. Our findings allow us to conclude that the alkylglycoside is a suitable candidate vector for renal targeting.
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PMID:Renal drug targeting using a vector "alkylglycoside". 986 53

The sulphonylurea drugs have been the mainstay of oral treatment for patients with diabetes mellitus since they were introduced. In general, they are well tolerated, with a low incidence of adverse effects, although there are some differences between the drugs in the incidence of hypoglycaemia. Over the years, the drugs causing the most problems with hypoglycaemia have been chlorpropamide and glibenclamide (glyburide), although this is a potential problem with all sulphonylureas because of their action on the pancreatic beta cell, stimulating insulin release. Other specific problems have been reported with chlorpropamide that occur only rarely, if at all, with other sulphonylureas. Hyponatraemia secondary to inappropriate antidiuretic hormone activity, and increased flushing following the ingestion of alcohol, have been well described. The progressive beta cell failure with time results in eventual loss of efficacy, as these agents depend on a functioning beta cell and are ineffective in the absence of insulin-producing capacity. Differences in this secondary failure rate have been reported, with chlorpropamide and gliclazide having lower failure rates than glibenclamide or glipizide. The reasons for this are unclear, but the more abnormal pattern of insulin release produced by glibenclamide may be partly responsible and, indeed, may explain the increased risk of hypoglycaemia with this agent. Previously reported increased mortality associated with tolbutamide therapy has not been substantiated, and more recent data have shown no increased mortality from sulphonylurea treatment. Indeed, benefit from glycaemic control, regardless of the agent used--insulin or sulphonylurea--was reported by the United Kingdom Prospective Diabetes Study. Nevertheless, there is still ongoing controversy in view of the experimental evidence, mainly from animal studies, of potential adverse effects on the heart from sulphonylureas, but these are difficult to extrapolate into clinical situations. Most of these studies have been carried out with glibenclamide, which makes comparison of possible risk difficult. Other cardiovascular risk factors may be modified by gliclazide, which seems unique among the sulphonylureas in this respect. Its reported haemobiological and free radical scavenging activity probably resides in the azabicyclo-octyl ring structure in the side chain. Reduced progression or improvement in retinopathy has been reported in comparative trials with other sulphonylureas, and the effect is unrelated to improvements in glycaemia. There are differences between the sulphonylureas in some adverse effects, risk of hypoglycaemia, failure rates and actions on vascular risk factors. As a group of drugs, they are very well tolerated, but differences in overall tolerability can be identified.
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PMID:Comparative tolerability of sulphonylureas in diabetes mellitus. 1078 25


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