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)

Bradykinin (BK) (Arg1-Pro2-Pro3-Gly4-Phe5-Ser6-Pro7-Phe8-Arg9) was degraded by rat brain synaptic membranes at a rate comparable to that found for Met-enkephalin, but approximately 40 times the rate for vasopressin and oxytocin. The catabolic pathway for BK and its metabolites was elucidated through the use of high performance liquid chromatography for metabolite identification and peptidase inhibitors for blocking specific cleavage sites. BK was hydrolyzed at three sites: at the -Phe5-Ser6- bond by metalloendopeptidase 24.15, at the -Pro7-Phe8- bond by an apparently novel peptidyl dipeptidase, and at the -Phe8-Arg9 bond by a carboxypeptidase B-like enzyme. Each enzyme contributed about equally to BK degradation under the assay conditions used. Some of the resulting metabolites were further hydrolyzed: BK(1-8) to BK(1-7) + Phe by a DFP inhibitable prolyl carboxypeptidase-like enzyme, BK(1-8) to BK(1-5) + BK(6-8) by metalloendopeptidase 24.15, BK(1-7) slowly to BK(1-5) by a second peptidyl dipeptidase which was captopril inhibited, and Phe-Arg to Phe + Arg by a bestatin-inhibited dipeptidase. A number of properties of the individual enzymes were determined including sensitivity to a variety of peptidase inhibitors. These results provide a starting point for investigating the potential physiological role of each enzyme in BK function in the brain.
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PMID:Degradation of bradykinin and its metabolites by rat brain synaptic membranes. 260 54

The effect of bradykinin on the neuroeffector junction of the isolated rat vas deferens was studied in tissues stimulated transmurally at a frequency of 0.15 Hz. Bradykinin caused two distinct and independent actions: it potentiated the magnitude of the muscular response to the electrically driven twitches and, in addition, contracted the smooth muscle generating an increased muscular tone. The former action is referred to as the neurogenic or presynaptic effect, whereas the latter effect is called the musculotropic or postjunctional action. The neurogenic effect was abolished by tetrodotoxin or tissue denervation either by cold storage or chemical sympathectomy after 6-hydroxydopamine administration. However, these procedures did not significantly modify the musculotropic potency of bradykinin. Both actions of the peptide are receptor-mediated, as minor structural modifications in the amino acid sequence caused significant changes in biological potency. In addition, the peptide analog, [Thi5,8-D-Phe7]-bradykinin, behaved as an agonist at the presynaptic site but as an antagonist at the muscular site. The most potent peptide analog to produce the neurogenic effect was Met-Lys-bradykinin followed by Lys-bradykinin and [Tyr8]-bradykinin. In contrast, the potency of these peptide analogs acting at the postsynaptic site was about the same. des Arg9 bradykinin and des Arg9-[Leu8]-bradykinin were inactive at the pre- and postjunctional site. The neurogenic action of bradykinin was not mimicked by angiotensin II, neurotensin, substance P or vasopressin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Identification of pre- and postsynaptic bradykinin receptor sites in the vas deferens: evidence for different structural prerequisites. 288 2

The role of the phosphoinositide turnover-protein kinase C pathway in mediating PDGF-stimulated c-myc expression and cell proliferation was studied. Both direct activators of kinase C (e.g. phorbol ester analogues) and hormones that activate kinase C via receptor-mediated phosphoinositide turnover (e.g. PDGF, bradykinin, or vasopressin) elicited a rapid increase in c-myc mRNA expression. Desensitization of the kinase C pathway by prolonged exposure to phorbol abolished the induction of c-myc by subsequent phorbol challenge and attenuated c-myc induction by PDGF and bradykinin, but did not affect PDGF-stimulated mitogenesis. Bradykinin and phorbol esters stimulated the same magnitude of c-myc expression as PDGF but elicited less than one-tenth the PDGF-induced mitogenic response. We conclude that stimulation of c-myc expression is a common response to a diverse group of agents that elicit phosphoinositide turnover and activate protein kinase C, and that neither activation of protein kinase C nor enhanced c-myc expression is sufficient for the mitogenic action of PDGF.
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PMID:c-myc gene expression is stimulated by agents that activate protein kinase C and does not account for the mitogenic effect of PDGF. 300 Jun 1

To evaluate a possible modulation by protein kinase C of hormonal, cAMP-mediated effects on renal epithelial cells, we studied the effect of protein kinase C activators and of bradykinin on intracellular cAMP accumulation in MDCK cells. A 15-min pretreatment of cells with phorbol 12-myristate 13-acetate or 1-oleoyl-2-acetylglycerol induced a dose-dependent inhibition of vasopressin-stimulated cAMP synthesis, but not of basal or glucagon-, prostaglandin E2-, and forskolin-stimulated cAMP generation. 4 alpha-Phorbol 12,13-didecanoate, inactive on protein kinase C, did not affect cAMP accumulation. Bradykinin (0.1-10 microM) also inhibited the stimulatory effect of vasopressin on cAMP synthesis in a concentration-dependent manner, but affected neither basal cAMP content, nor its stimulation by glucagon, prostaglandin E2 and forskolin. The effect of activators of protein kinase C and of bradykinin occurred while renal prostaglandin synthesis was blocked with indomethacin. The inhibitory effect of protein kinase C activators and bradykinin on cAMP generation was reversed by the protein kinase C inhibitor H7, was enhanced by monensin, one effect of which is to block the recycling of membrane receptors, and persisted when the GTP-binding protein N1 was blocked with 1 mM Mn2+. Our data suggest that: protein kinase C can modulate the tubular effects of vasopressin by inhibiting cAMP generation; this effect is not mediated by renal prostaglandins, and might result from a direct action on the vasopressin receptor, or on its coupling with Ns; the modulation by bradykinin of vasopressin effects are likely to be exerted, at least partly, through activation of protein kinase C.
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PMID:Protein kinase C activators and bradykinin selectively inhibit vasopressin-stimulated cAMP synthesis in MDCK cells. 303 98

Our previous studies in cortical collecting ducts isolated from rat kidneys have shown that vasopressin increases both sodium absorption and potassium secretion, while bradykinin inhibits sodium absorption without affecting potassium transport. To determine which anions are affected by these agents, we perfused cortical collecting ducts from rats treated with deoxycorticosterone and measured net chloride flux, net bicarbonate flux (measured as total CO2), transepithelial voltage, and the rate of fluid absorption. Arginine vasopressin (10(-10) M in the peritubular bath) caused a sustained sixfold increase in net chloride absorption and a two- to threefold increase in the magnitude of the lumen negative transepithelial voltage. Before addition of vasopressin, the tubules secreted bicarbonate. Vasopressin abolished the bicarbonate secretion, resulting in net bicarbonate absorption (presumably due to proton secretion) in many tubules. Bradykinin (10(-9) M added to the peritubular bath) caused a reversible 40% inhibition of net chloride absorption, but did not affect the transepithelial voltage or the bicarbonate flux. We concluded: (a) that arginine vasopressin stimulates absorption of chloride and inhibits bicarbonate secretion (or stimulates proton secretion) in the rat cortical collecting duct; and (b) that bradykinin inhibits net chloride absorption in the rat cortical collecting duct without affecting transepithelial voltage or bicarbonate flux. Combining these results with the previous observations on cation fluxes described above, we conclude that bradykinin inhibits electroneutral NaCl absorption (or stimulates electroneutral NaCl secretion) in the rat cortical collecting duct.
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PMID:Effects of vasopressin and bradykinin on anion transport by the rat cortical collecting duct. Evidence for an electroneutral sodium chloride transport pathway. 308 Apr 71

We investigated the role of calcium in basal, ionophore- and hormone-stimulated prostaglandin E2 (PGE2) production by rat inner medullary collecting tubule cells. Basal PGE2 production is significantly decreased in the absence of calcium (4.49 +/- 0.79 vs. 19.99 +/- 3.47 pg/micrograms protein/h, p less than 0.001). No further increment is seen at 4 mM calcium. The ability of the calcium ionophore A23187 to stimulate PG production is proportional to the amount of calcium present in the extracellular space. Bradykinin is a potent stimulus to PG production even in the virtual absence of calcium while arginine vasopressin has only a modest effect. Neither bradykinin nor arginine vasopressin exhibit any further PG stimulation at 1 mM calcium; both bradykinin and arginine vasopressin increase PGE2 production significantly when calcium is increased to a supraphysiologic level. The data suggests an important role for intracellular rather than extracellular calcium in the control of PG production. Bradykinin but not vasopressin display significant calcium-independent stimulatory effects on PG synthesis.
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PMID:Control of prostaglandin E2 synthesis in cultured rat inner medullary collecting tubule cells: the role of calcium. 310 Sep 18

The production of prostaglandins by rat renal tubular cells and by rat vascular smooth muscle cells (VSMC) in response to vasoactive hormones was examined. A superfusion technique was used to stimulate collagenase-dispersed renal cortical or medullary tubular cells and trypsinized rat aortic smooth muscle cells with vasoactive hormones and ANF. All cell types responded promptly to the stimuli in a dose-dependent manner. Renal tubular cells produced mainly PGE2, less PGF2 alpha and no 6-keto-PGF1 alpha, while VSMC produced exclusively 6-keto-PGF1 alpha. This production of PG was strictly dependent on the presence of extracellular Ca2+ and was not inhibited by antagonists of voltage-dependent Ca2+-channels. Angiotensin II (Ang II) was active on cortical tubular cells and VSMC. Sar1-Ala8-angiotensin II blocked this action. Arginine-vasopressin (AVP acted on medullary tubular cells and VSMC and its effect was inhibited by selective V1-antagonists. The V2-agonist dDAVP had no effect on PG production. A clear distinction between V1-receptor mediated PG release and V2-receptor mediated cAMP extrusion was observed in medullary tubular cells. Bradykinin was a weak agonist on medullary tubular cell. The synthetic (1-24) atrial natriuretic peptide did not prevent 6-keto-PGF1 alpha release induced by Ang II or AVP in VSMC nor the PGE2 release in cortical tubular cells induced by Ang II.
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PMID:The regulation of prostaglandins by vasoactive hormones in renal tubular and vascular smooth muscle cells. 312 55

Bradykinin elicits a complex response in the renal glomerulus which includes a reduction in the glomerular capillary ultrafiltration coefficient. To elucidate the biochemical mechanism of this response, we investigated calcium signalling in rat renal glomerular mesangial cells in culture using the calcium-sensitive fluorescent dye, Indo-1. Bradykinin was found to cause a concentration-dependent transient rise in cytosolic free calcium followed by a sustained slower secondary rise. The bradykinin response persisted with acute removal of extracellular calcium using EGTA, indicating that calcium entry from outside the cell did not mediate this primary response. Prolonged exposure to EGTA, which reduced intracellular stores, eliminated the calcium response to bradykinin but not to vasopressin, indicating differential sensitivity to intracellular calcium stores of these two hormonal responses. In agreement, prior stimulation with vasopressin significantly attenuated the response to bradykinin, but the converse did not occur. Aluminum fluoride and pertussis toxin were used to investigate the possible involvement of a guanyl nucleotide regulatory protein in signal transduction. Aluminum fluoride induced a transient rise in cytosolic calcium that was abrogated by prior exposure of the cells to pertussis toxin. This demonstrates the effectiveness of pertussis toxin and the presence of a calcium-signalling pathway susceptible to pertussis toxin in these cells. In contrast, the responses to bradykinin and vasopressin were unaffected by pertussis toxin. We conclude that bradykinin stimulates release of calcium from intracellular stores in glomerular mesangial cells via a pertussis toxin insensitive pathway. This mesangial response provides a direct biochemical basis for the bradykinin-induced fall in glomerular capillary ultrafiltration coefficient which has been observed in vivo.
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PMID:Bradykinin stimulates a rise in cytosolic calcium in renal glomerular mesangial cells via a pertussis toxin insensitive pathway. 337 May 34

WRK 1 cells were labelled to equilibrium with 2-myo-[3H]inositol and stimulated with vasopressin. Within 3 s of hormone stimulation there was a marked accumulation of 3H-labelled InsP2 and InsP3 (inositol bis- and tris-phosphate), but not of InsP (inositol monophosphate). There was an associated, and rapid, depletion of 3H-labelled PtdInsP and PtdInsP2 (phosphatidylinositol mono- and bis-phosphates), but not of PtdIns (phosphatidylinositol), in these cells. Some 4% of the radioactivity in the total inositol lipid pool of WRK 1 cells was recovered in InsP2 and InsP3 after 10 s stimulation with the hormone. The selectivity of the vasopressin receptors of WRK 1 cells for a variety of vasopressin agonists and antagonists revealed these to be of the V1a subtype. There was no receptor reserve for vasopressin-stimulated inositol phosphate accumulation in WRK 1 cells. The accumulation of inositol phosphates was enhanced in the presence of Li+ions. Half-maximal accumulation of InsP, InsP2 and InsP3 in vasopressin-stimulated cells was observed with 0.9, 3.0 and 3.6 mM-Li+ respectively. Bradykinin and 5-hydroxytryptamine also provoked inositol phosphate accumulation in WRK 1 cells. The effects of sub-optimal concentrations of bradykinin and vasopressin upon inositol phosphate accumulation were additive, but those of optimal concentrations of the hormones were not.
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PMID:Stimulation, by vasopressin and other agonists, of inositol-lipid breakdown and inositol phosphate accumulation in WRK 1 cells. 382 39

Release of tissue plasminogen activator into the circulation of rats in response to intravascular injections of vasoactive agents is studied by using a sensitive and specific clot lysis assay. Intra-arterial bradykinin elicits a rapid and transient rise in circulating plasminogen activator, which is maximum within one minute and is cleared within four to eight minutes. The plasminogen activator is fibrin dependent and is neutralized by an antiserum to human tissue-type plasminogen activator. Bradykinin is 1,000-fold more potent than the other agonists tested, which include histamine, norepinephrine, epinephrine, eledoisin-related peptide, arginine-vasopressin, lysine-vasopressin, desmopressin acetate, carbachol, and acetylcholine. Potency of bradykinin is related to its amino acid sequence. Sequential infusions of bradykinin produce a tachyphylactoid response that could be overcome by increasing the dose of the sequential bradykinin challenge. It is concluded that the characteristics of the responses to bradykinin and other agents in vivo differ significantly from those observed in isolated tissue preparations.
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PMID:Tissue plasminogen activator release in vivo in response to vasoactive agents. 392 59


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