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

The effect of forskolin, added either before or 5 min after the onset of potassium-evoked release of vasopressin from isolated neurointermediate lobes of the rat has been investigated. A low concentration of forskolin (1 microM), added before stimulation, enhanced the potassium-evoked release of vasopressin throughout two successive 5 min periods of stimulation. Higher concentrations of forskolin (10-80 microM) produced no effect on the potassium-evoked release of hormone during the first 5 min of stimulation, but inhibited release during the second 5 min period. When added 5 min after the onset of potassium stimulation, forskolin (1-80 microM) reduced the amount of vasopressin released during the remaining 5 min of stimulation. Forskolin produced a concentration-dependent increase in cyclic AMP during both the control and potassium stimulation periods. The amount of cyclic AMP generated by forskolin during potassium stimulation was less than that produced during the corresponding control periods.
 ...
PMID:Forskolin: its effects on potassium-evoked release of vasopressin from the rat neurohypophysis. 299 49

Dopamine inhibits and serotonin stimulates adenylate cyclase activity in a neuroblastoma X Chinese hamster brain explant cell line (NCB-20). The inhibition of cyclic AMP accumulation by dopamine was blocked by pretreatment of the cells with pertussis toxin. Carbachol and bradykinin stimulated the accumulation of water-soluble inositol phosphates whereas thyrotropin-releasing hormone, vasopressin, neurotensin, and phenylephrine were without effect. Dopamine and serotonin had no significant effect on carbachol-induced phosphoinositide hydrolysis or the levels of the parent lipids within the membrane. Forskolin induced a much larger stimulation of cyclic AMP than did serotonin, and caused an increase in the levels of phosphatidylinositol-4-phosphate and phosphatidyl inositol-4,5-bisphosphate in the cell membrane.
 ...
PMID:Activation of dopamine receptors does not affect phosphoinositide turnover in NCB-20 cells. 303 93

Radiation inactivation was used to examine the mechanism of activation of adenylate cyclase in the cultured renal epithelial cell line LLC-PK1 with hormonal (vasopressin) and nonhormonal (GTP, forskolin, fluoride, and chloride) activating ligands. Intact cells were frozen, irradiated at -70 degrees C (0-14 Mrad), thawed, and assayed for adenylate cyclase activity in the presence of activating ligands. The ln (adenylate cyclase activity) vs. radiation dose relation was linear (target size 162 kDa) for vasopressin- (2 microM) stimulated activity and concave downward for unstimulated (10 mM Mn2+), NaF- (10 mM) stimulated, and NaCl- (100 mM) stimulated activities. Addition of 2 microM vasopressin did not alter the ln activity vs. dose relation for NaF- (10 mM) stimulated activity. The dose-response relations for adenylate cyclase activation and for transition in the ln activity vs. dose curve shape were measured for vasopressin and NaF. On the basis of our model for adenylate cyclase subunit interactions reported previously [Verkman, A. S., Skorecki, K. L., & Ausiello, D. A. (1986) Am. J. Physiol. 260, C103-C123] and of new mathematical analyses, activation mechanisms for each ligand are proposed. In the unstimulated state, equilibrium between alpha beta and alpha + beta favors alpha beta; dissociated alpha binds to GTP (rate-limiting step), which then combines with the catalytic (C) subunit to form active enzyme. Vasopressin binding to receptor provides a rapid pathway for GTP binding to alpha. GTP and its analogues accelerate the rate of alpha GTP formation. Forskolin inhibits the spontaneous deactivation of activated C. Activation by fluoride may occur without alpha beta dissociation or GTP addition through activation of C by an alpha beta-F complex.
 ...
PMID:Mechanisms of nonhormonal activation of adenylate cyclase based on target analysis. 376 98

Forskolin is a unique diterpene that may directly activate the catalytic subunit of adenylate cyclase. We therefore examined the effect of 50 microM forskolin on osmotic water permeability in rabbit cortical collecting tubules perfused in vitro. Forskolin increased net volume flux (Jv, from 0.30 to 1.22 nl/mm/min, P less than 0.02) in all tubules. The hydro-osmotic effect of forskolin was similar with respect to magnitude and time course to that produced by a maximal dose (250 microU/ml) of arginine vasopressin. An additive effect on Jv and Lp was not observed when maximal concentrations of forskolin and arginine vasopressin were given simultaneously. The compound d(CH2)5Tyr(Et) VAVP, which noncompetitively inhibits the vasopressin receptor, significantly reduced collecting tubular hydro-osmotic response to arginine vasopressin. In contrast, the hydro-osmotic response to forskolin was maintained in the presence of d(CH2)5 Tyr(Et)VAVP. However, the hydro-osmotic response to forskolin could be inhibited by 1.0 microM guanine 5'-(beta,gamma-imido) triphosphate (GppNHp) and by the calmodulin inhibitor N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7). These results demonstrate that forskolin exerts an hydro-osmotic effect in the mammalian nephron which occurs independent of the vasopressin receptor. Guanine nucleotide regulatory proteins may modulate the osmotic water permeability effect of forskolin. Finally, calmodulin is required for full expression of the effect of forskolin to increase osmotic water flux.
 ...
PMID:Forskolin increases osmotic water permeability of rabbit cortical collecting tubule. 654 43

Isolated neurointermediate lobes of rat pituitaries were incubated in Krebs solution. The vasopressin release evoked by electrical stimulation (0.2 ms, 80 V, 15 Hz, 10 s trains at 10 s intervals for a total of 10 min) was completely inhibited by tetrodotoxin. Isoprenaline increased the evoked vasopressin release to a maximum of 60% (EC50 10 nM) and this effect was antagonized surmountably by propranolol. Forskolin increased the vasopressin release by 98%. These results suggest the presence within the neurohypophysis of a beta-adrenoceptor-linked adenylate cyclase facilitating vasopressin secretion.
 ...
PMID:Isoprenaline and forskolin increase evoked vasopressin release from rat pituitary. 688 72

Intracellular pH (pHi), apical membrane potential (Va), and fractional apical membrane resistance (FRa) were measured in principal cells of isolated frog skin (Rana pipiens) with double-barreled microelectrodes under short-circuit conditions. Basolateral exposure to 10 mU/ml arginine vasotocin (AVT) depolarized Va by 30 mV, decreased FRa by 33%, increased short-circuit current (Isc) by 17 microA, and increased pHi by 0.17 pH units. The response of Va, Isc, and pHi occurred concurrently. Forskolin, theophylline, and 8-(4-chlorophenyl-thio)-adenosine 3',5'-cyclic monophosphate caused similar changes in Va, Isc, and pHi. The enhanced response of Isc, Va, and FRa to short pulses of apical amiloride applied during AVT or cAMP exposure suggests an increase in apical Na+ conductance. The presence of cAMP agonists also enhanced the response of pHi to amiloride. We conclude that the AVT- and cAMP-induced increase in Na+ transport across the apical cell membrane is associated with a change in pHi. These data are consistent with the hypothesis that changes in pHi may play a role in the second messenger cascade initiated by the antidiuretic hormone.
 ...
PMID:Na+ transport and pH in principal cells of frog skin: effect of antidiuretic hormone. 804 13

The effect of insulin on water and urea transport was examined in normal isolated rat inner medullary collecting duct (IMCD). Hydraulic conductivity (Lp, x 10(-6) cm.atm-1.s-1), diffusional water permeability (Pdw, x 10(-5) cm/s) and [14C]urea permeability (x 10(-5) cm/s) were studied at 37 degrees C and pH 7.4. Insulin (6 x 10(-8) M; 200 microU/ml) added to the bath fluid enhanced Lp from 0.40 +/- 0.10 to 1.21 +/- 1.40 (P < 0.01) and Pdw from 42.40 +/- 3.40 to 58.50 +/- 5.00 (P < 0.02) and also stimulated Lp in a dose-dependent manner. In the presence of antidiuretic hormone (ADH)-stimulated Pdw (10 microU/ml), insulin increased Pdw even more. Prostaglandin E2 (10(-5) M) added to the bath reversibly increased insulin-induced Lp. Forskolin (10(-4) M) blocked the action of insulin. Colchicine (10(-4) M) and V1-receptor antagonist (10(-4) M) inhibited the development but not the maintenance of insulin-stimulated Pdw. Vanadate (2.5 x 10(-6) M) enhanced Pdw. Polymyxin B (10(-5) M) inhibited the insulin-stimulated Pdw, whereas in a glucose-free medium insulin did not enhance Pdw. Urea transport was not affected by insulin. These data suggest that insulin may enhance water transport, probably by stimulating glucose transporters, which would serve as a water channel. We cannot rule out the possibility that insulin may be eliciting existing ADH-like mechanisms of water transport, beyond the microtubule step, to establish water transport.
 ...
PMID:Effect of insulin on water and urea transport in the inner medullary collecting duct. 816 Jul 87

Cisplatin is an antineoplastic agent. Several nephrotoxic effects are associated with its use including chronic and acute renal failure, renal magnesium wasting, and polyuria. We have investigated polyuria in groups of rats treated with cisplatin at doses of 2.5 and 5 mg/kg body weight given once weekly for 3 weeks to determine possible mechanisms of this impairment. After cisplatin administration, glomerular filtration rate was reduced and significant increases in sodium and water loss were also seen. These changes were associated with decreases in urinary cAMP. Inner medullary collecting duct (IMCD) cells were removed from these animals and were stimulated with graded doses of vasopressin. Cells from cisplatin-treated rats showed an impaired response in cAMP generation to vasopressin stimulation as compared to cells from normal animals. To determine more precisely the site of impairment, the adenylate cyclase complex of the IMCD cells was further studied with forskolin and NaF. Forskolin was used to probe the catalytic unit activating adenylate cyclase, and NaF the guanine nucleotide regulatory protein (G protein). In response to forskolin, cells from cisplatin-treated rats and normal rats responded similarly in generating cAMP. However, following NaF, the cAMP response was blunted in the cells from the cisplatin rats. These results suggested that the catalytic unit was not injured by cisplatin (forskolin study) but the G protein was (NaF). In conclusion, the present study suggests that the polyuria seen following cisplatin administration is associated with an end-organ resistance to vasopressin manifested by reduced cAMP generation, secondary in part or whole to a defect at the level of the G protein.
 ...
PMID:Mechanism of polyuria after cisplatin therapy. 830 21

We investigated the effects of human calcitonin gene-related peptide (CGRP) on isolated rabbit hearts to evaluate the mechanisms responsible for the vasodilatory action of the peptide on the coronary district, monitoring contemporaneously the effects on left ventricular pressure (LVP) and heart rate (HR). We also evaluated the reactivity of the human internal mammary artery (IMA) to excitatory drugs acting with different mechanisms and the inhibitory response to CGRP in comparison with the commonly used vasodilatory agents. The peptide induced a slight inhibitory effect on the basal coronary perfusion pressure (CPP), whereas it was ineffective on the inotropism and chronotropism. A more detectable coronary vasodilation was evident when CPP was increased by spasmogenic agents [vasopressin, methoxamine, Bay K 8644, and prostaglandin F2 alpha (PGF2 alpha)]. This inhibitory effect was dose dependent (10(-11)-10(-8) M) and apparently not specific, occurring to the same extent on different stimuli. Forskolin (10(-8) M), an adenylate-cyclase activator, and indomethacin (1.4 x 10(-5) M), a cyclooxygenase inhibitor, did not modify the spasmolytic activity of CGRP on precontracted coronary smooth muscle. The experiments performed on the segments of IMA, used for myocardial revascularization of patients affected by coronary diseases, have shown an evident spasmolytic action of CGRP on increased vascular tone induced by KCl (90 mM), noradrenaline (10(-5) M), serotonin (10(-6) M), and angiotensin II (10(-6) M). These inhibitory responses of CGRP on the spasmogenic compounds disappeared when the endothelial function of IMA, validated by the acetylcholine test, was abolished by mechanical ablation. A series of IMA segments was incubated (30 min) with N(G)-monomethil-L-arginine (L-NMMA), which inhibits nitric oxide (NO) synthase. In these experiments, the peptide failed to induce the vasodilation, suggesting that its action may be related to synthesis of NO. All these results show that CGRP is able to induce a potent vasodilatory action on different vessels of humans (internal mammary artery) and animals (rabbit coronary arteries). In particular the data obtained from IMA demonstrated that the vasorelaxant effect was related to synthesis of NO, one of the most studied endothelium-derived relaxing factors (EDRFs).
 ...
PMID:Mechanism of action of human calcitonin gene-related peptide in rabbit heart and in human mammary arteries. 915 55

To study the transcriptional regulation of the vasopressin gene in vitro, 3 kb of the 5' regulatory region of the rat vasopressin gene was isolated and subcloned, along with a series of various deletion mutants, into vectors containing the luciferase reporter gene. After transfecting these genes transiently into the human choriocarcinoma cell line JEG-3 along with a glucocorticoid receptor (GR) expression vector, transcriptional activity was quantitated using the luciferase assay. Forskolin, 8-bromo-cAMP, and protein kinase A catalytic subunit expression all markedly increased transcription from the 3-kb promoter. Analyses with deletion mutants of the promoter showed that two cAMP-responsive element (CRE)-like sequences (-227 to -220 bp and -123 to -116 bp) contribute to this positive regulation. Expression of KCREB, a dominant negative mutant of the cAMP-responsive element binding protein (CREB), suggested the involvement of CREB. Transfection of the activator protein 2 (AP2) DNA consensus sequence partially blocked transcription. Dexamethasone suppressed forskolin-stimulated expression. The negative effect of glucocorticoid was GR dependent and may be mediated by a mechanism not involving GR binding to DNA because it was independent of the putative glucocorticoid-responsive element previously reported in the vasopressin promoter (-622 to -608 bp) and was preserved in the shorter promoter constructs in which no glucocorticoid-responsive element-like sequence was found. Our data suggest that several trans-acting factors including CREB, AP2, and GR are likely to be involved in vasopressin gene transcription and that the positive and negative regulation of vasopressin gene transcription is complex.
 ...
PMID:Positive and negative regulation of the rat vasopressin gene promoter. 938 10


<< Previous 1 2 3 4 Next >>