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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A peptide analogue of [8-arginine]vasopressin (AVP) with Lys substituted for Gly at position 9 ([d(CH2)5Tyr(Me)2LysNH2(9)]AVP; ALVP) has been synthesized as a precursor for the production of heterofunctional vasopressin receptor ligands. Three heterofunctional ligands have been prepared by attaching biotin and a photoreactive cross-linker capable of iodination, either alone or in combination, to the epsilon-amino group of Lys at position 9 in ALVP. The binding characteristics of these novel ligands have been determined at the V1a and V2 vasopressin receptors by employing membrane preparations of rat liver and kidney respectively. All of the analogues synthesized during the course of this study bound selectively, and with high affinity, to the V1a vasopressin receptor subtype. Our results demonstrate that the strategies described in this paper provide a convenient means of synthesizing heterofunctional vasopressin receptor ligands with preservation of subtype-specific, high affinity binding characteristics. These parameters establish the potential value of the analogues as probes for investigating V1a receptor structure and function.
J Mol Endocrinol 1992 Oct
PMID:Design and synthesis of heterofunctional V1a-selective vasopressin receptor ligands with lysine at position 9. 141 83

The effects of adding oxytocin (OT) and arginine-vasopressin (AVP) on progesterone and estradiol-17 beta secretion by bovine granulosa cells in culture were studied. The influence of these steroids on OT and AVP release was also evaluated. OT (1, 10, 100 or 1000 mIU/ml) stimulates both progesterone and estradiol output. Small doses (10 pM/ml) of exogenous progesterone or estradiol stimulated a surge in OT, while the intermediate doses (100 or 1000 pM/ml) had no influence, and large doses (10,000 pM/ml) inhibited OT secretion by granulosa cells. Thus, a potential regulatory loop between OT and steroid hormone release by granulosa cells was demonstrated. Stimulation of a surge in steroids by OT, activation of OT release by small doses of steroids and inhibition of OT secretion by excess steroids may suggest the existence of a feedback mechanism regulating these hormones production. Addition of AVP (1, 10, 100 or 1000 pM/ml) inhibited progesterone and stimulated a surge in estradiol, while steroid hormones did not induce AVP release. These data suggest the regulation of ovarian steroidogenesis by AVP, feedback influences are less likely.
J Steroid Biochem Mol Biol 1992 Nov
PMID:The interrelationships between nonapeptide and steroid hormones secretion by bovine granulosa cells in vitro. 141 88

We have studied the effects of vasopressin and tetradecanoyl phorbol acetate (TPA) on cytosolic free Ca2+ ([Ca2+]i) and insulin release in HIT-T15 beta-cells. Saturable binding of [3H] [Arg8]-vasopressin to HIT cell microsomes indicated a single class of receptors with a dissociation constant (Kd) of 2.5 nM and a total number of binding sites (Bmax) equal to 120 fmol/mg protein. [Arg8]-vasopressin (0.1-100 nM) elicited dose-dependent insulin release from HIT cells by up to 25-fold. This increase was dependent on the presence of extracellular glucose and was blocked by omission of extracellular Ca2+ or addition of verapamil. The stimulation was biphasic; a rapid but short-lived large increase in release was followed by a smaller sustained rise. Vasopressin also evoked a marked, concentration-dependent increase in [Ca2+]i which was also biphasic; an initial spike was followed by a sustained elevation. This increase also required glucose and was blocked by the absence of extracellular Ca2+ or the addition of verapamil. Pretreatment of the cells with TPA overnight to deplete protein kinase C activity did not affect the [Ca2+]i or insulin responses to vasopressin. However, short-term exposure to TPA markedly reduced glucose-induced steady-state [Ca2+]i, despite potentiating glucose-stimulated insulin release sevenfold, and blocked the [Ca2+]i increase induced by vasopressin. These inhibitory effects of TPA were absent in protein kinase C-depleted cells and were prevented by staurosporine. TPA had no significant effect on vasopressin-induced insulin release. Vasopressin did not modify the activity of ATP-sensitive K+ channels.(ABSTRACT TRUNCATED AT 250 WORDS)
J Mol Endocrinol 1992 Apr
PMID:Stimulation of insulin release by vasopressin in the clonal beta-cell line, HIT-T15: the role of protein kinase C. 151 19

Excitable cells often display rapid coordination of hormone-induced intracellular calcium signals. Calcium elevations that begin in a single epithelial cell also may spread to adjacent cells, but coordination of hormone-induced signals among epithelial cells has not been described. We report the use of confocal microscopy to determine the inter- and intracellular distribution of cytosolic calcium in isolated rat hepatocyte couplets, an isolated epithelial cell system in which functional polarity is maintained. Both vasopressin and phenylephrine evoked sequential coordinated calcium signals in the couplets, even during cytosolic calcium oscillations. The coupling was abolished by closure of intercellular gap junction channels by treatment with octanol. These observations demonstrate that hormone-induced intracellular calcium signals are coordinated among hepatocytes and suggest that gap junction channels mediate this intercellular integration of tissue responsiveness.
Mol Biol Cell 1992 Jan
PMID:Coordination of hormone-induced calcium signals in isolated rat hepatocyte couplets: demonstration with confocal microscopy. 155 Sep 53

The effect of corticosterone injection and of acute and repeated stress on rat liver cytosol glucocorticoid receptor was studied to ascertain whether corticosterone-induced glucocorticoid receptor (GR) regulation also takes place in intact animals as it does in adrenalectomized ones. Adult male rats were exposed to six different stressors (swimming, 10 mg/kg histamine i.p., 500 mU/kg vasopressin s.c., heat, immobilization and cold) acutely or three times daily for 18 days (repeated stress). Each of the stressors applied acutely provoked a pronounced increase of plasma corticosterone with subsequent induction of hepatic tyrosine aminotransferase activity. Depletion of cytosol receptor was however only noticed after swimming and histamine injection. On the other hand, sustained hypersecretion of corticosterone evoked by repeated stress significantly reduced the number of GR in rat liver cytosol without any change in Kd. It is concluded that in the presence of intact adrenal glands cytosol receptors are more resistant to corticosterone-induced depletion than in their absence. Further, repeated stress causes down-regulation of GR in the liver, most probably by sustained corticosterone secretion, yet the effect of other stress factors cannot be excluded.
J Steroid Biochem Mol Biol 1992 Jun
PMID:Stress-induced changes of glucocorticoid receptor in rat liver. 161 78

Endothelin (ET) receptors are present in pituitary cells and stimulate hormone release through the phosphoinositide/Ca2+ signaling system. In pituitary cell suspensions, ET caused [Ca2+]i elevations of much higher amplitudes than those induced by other vasoactive hormones, including angiotensin II, vasopressin, and noradrenalin. The action of ET was coupled to rapid and transient activation of exocytosis in gonadotrophs, thyrotrophs, somatotrophs, and lactotrophs. In contrast, angiotensin II did not stimulate luteinizing hormone release, and luteinizing hormone responses to vasopressin and noradrenalin were very small. Single gonadotrophs exhibited three types of [Ca2+]i responses to increasing doses of ET, (a) subthreshold responses, with amplitude modulation; (b) threshold-oscillatory responses, with frequency modulation; and (c) threshold-biphasic responses, as the summation of single Ca2+ spikes. The same [Ca2+]i patterns were also seen in gonadotropin-releasing hormone (GnRH)-stimulated cells. In the presence of [Ca2+]e, the amplitudes of the Ca2+ spikes progressively decreased during continuous stimulation with ET or GnRH, reaching the nonoscillatory plateau level after 200-400 sec of stimulation. In cells stimulated with GnRH, subsequent exposure to ET, GnRH, or ionomycin during the plateau phase did not elicit further increases in [Ca2+]i, whereas cells stimulated with ET responded partially to all three agents. In addition, cells exposed to ET or GnRH for 30 min, followed by a 30-min recovery period, were able to mount a full [Ca2+]i response to GnRH, but not to ET-1. Similarly, both peptides elicited rapid increases in LH release, with comparable potencies, but the response to ET decreased much more rapidly during sustained stimulation and gonadotrophs became refractory to further ET stimulation. This is in part attributable to rapid endocytosis of ET receptors during continuous agonist stimulation. These data indicate that ET exerts potent but transient secretory actions in several pituitary cell types and is a potential regulator of gonadotropin release. The initial receptor-coupling events in both ET- and GnRH-stimulated cells are similar, but the differences observed during continuous or repetitive stimulation indicate that the ET receptor pathway undergoes rapid desensitization that is critical in determining the distinct cellular responses to the two peptides.
Mol Pharmacol 1991 Jun
PMID:Calcium signaling and secretory responses in endothelin-stimulated anterior pituitary cells. 164 50

Endothelin-1 (ET-1) is a potent, vasoconstrictive peptide isolated from culture media of vascular endothelial cells. The binding of ET-1 to membrane preparations from rat and bovine lung was studied using radioiodinated ET-1 (125I-ET-1). With both membrane preparations, 125I-ET-1 showed saturable binding to a single class of high affinity sites. Scatchard analysis of the binding data gave dissociation constants (Kd) for ET-1 of 0.22 nM and 0.15 nM, and receptor densities (Bmax) of 6.1 pmol/mg and 2.7 pmol/mg for rat and bovine lung membranes, respectively. Photo-reactive radioiodinated ET-1, N epsilon 9-azidobenzoyl-125I-ET-1, was synthesized and purified as a mono-reactive affinity labeling reagent. This reagent was used for affinity labeling of ET-1 receptor in bovine and rat lung membranes. Photoaffinity labeling followed by sodium dodecyl sulfate gel electrophoresis and autoradiography gave a radiolabeled protein band with an apparent Mr of 34,000 in both membrane preparations. The labeling of this protein band was inhibited by cold ET-1 in a concentration-dependent manner. Labeling was not abolished by unrelated peptides such as angiotensin II and [Arg8]-vasopressin, or by structurally related bee venom apamin. These results indicate that the ET-1 receptor or its ligand binding subunit consists of a 34,000 Da polypeptide.
Mol Cell Endocrinol 1991 Aug
PMID:Affinity labeling of endothelin receptors in bovine and rat lung membranes by N epsilon 9-azidobenzoyl-125I-endothelin-1. 165 62

Oxytocin (OT) and V1 vasopressin (VP) receptors are present simultaneously in several tissues, including the uterus. In myometrium these receptors mediate contractility, while in endometrium they mediate the release of other uterotonic substances as endothelin (ET). In rabbit myometrium, estrogens increase, while progesterone blunts neurohypophysial hormone receptors. However, the action of sex steroids on OT and V1 VP receptors differs in terms of the ED50 and maximal effect. Therefore, at parturition, only OT receptors show a dramatic rise, while V1 VP receptors do not change, suggesting a major role for OT in labor. ET is a potent stimulator of uterine activity acting through specific receptors present on myometrial cells. These receptors as well as the endometrial localization of ET are modulated by sex steroids, indicating that ET might represent a paracrine regulator of uterine activity. In humans, OT but not V1 VP receptors increase as pregnancy progresses, confirming the primary relevance of OT in timing delivery.
J Steroid Biochem Mol Biol 1991
PMID:Steroid modulation of oxytocin/vasopressin receptors in the uterus. 165 85

The present study examines the effect of reduction of protein kinase C (PKC) activity, as induced by either phorbol ester (PMA) down-regulation or staurosporine inhibition, on the secretion of ACTH from cultured anterior pituitary (AP) cells. Short-term (3 h) exposure of cells to 5 nM PMA resulted in almost complete desensitization to both PMA and vasopressin (AVP), while there was only a minor incidence on the effect of corticotropin-releasing factor (CRF). In contrast, long-term (12-24 h) exposure of cells to PMA, as well as pretreatment with staurosporine, dramatically reduced the stimulatory influence of CRF. This was shown not to be due to a decline in ACTH cells' stores, nor to the toxicity of phorbol ester or to a negative autofeedback of ACTH. Pretreatment of corticotrophs with PMA failed to dampen the CRF-induced cyclic AMP formation, while it caused a decline in the effects of forskolin and 8-bromoadenosine cyclic AMP. Stimulated ACTH secretion subsequent to either veratridine- or high K(+)-induced cell depolarization was likewise decreased. We conclude that in corticotrophs the stimulatory action of not only AVP, but also of that of CRF on ACTH secretion strongly relies on PKC activity. In the case of CRF, however, this may not be a primary consequence of receptor occupation, as evidence suggests an indirect relationship which may involve PKC regulation of Ca2+ channels and/or the ion's intracellular messenger function.
Mol Cell Endocrinol 1991 May
PMID:Inhibition of protein kinase C activity in cultured pituitary cells attenuates both cyclic AMP-independent and -dependent secretion of ACTH. 166 63

Cellular responses to epidermal growth factor (EGF) are dependent on the tyrosine-specific protein kinase activity of the cell-surface EGF receptor. Previous studies using WB rat liver epithelial cells have detected at least 10 proteins whose phosphotyrosine (P-Tyr) content is increased by EGF. In this study, we have examined alternate modes of activating tyrosine phosphorylation. Treatment of WB cells with hormones linked to Ca2+ mobilization and protein kinase C (PKC) activation, including angiotensin II, [Arg8]vasopressin, or epinephrine, stimulated rapid (less than or equal to 15-s) and transient increases in the P-Tyr content of several proteins (p120/125, p75/78, and p66). These proteins, detected by anti-P-Tyr immunoblotting, were similar in molecular weight to a subset of EGF-sensitive P-Tyr-containing proteins (P-Tyr-proteins). The increased P-Tyr content was confirmed by [32P]phosphoamino acid analysis of proteins recovered by anti-P-Tyr immunoprecipitation. Elevating intracellular [Ca2+] with the ionophore A23187 or ionomycin or with the tumor promoter thapsigargin mimicked the effects of hormones on tyrosine phosphorylation, whereas treatment with a PKC-activating phorbol ester did not. In addition, responses to angiotensin II were not diminished in PKC-depleted cells. Ca2+ mobilization, measured by fura-2 fluorescence, was coincident with the increase in tyrosine phosphorylation in response to angiotensin II or thapsigargin. Loading cells with the intracellular Ca2+ chelator bis-(o-aminophenoxy)ethane-N ,N ,N' , N'-tetraacetic acid (BAPTA) inhibited the appearance of all P-Tyr-proteins in response to angiotensin II, thapsigargin, or ionophores, as well as two EGF-stimulated P-Tyr-proteins. The majority of EGF-stimulated P-Tyr-proteins were not affected by BAPTA. These studies indicate that angiotensin II can alter protein-tyrosine phosphorylation in a manner that is secondary to, and apparently dependent on, Ca2+ mobilization. Thus, ligands such as EGF and angiotensin II, which act through distinct types of receptors, may activate secondary pathways involving tyrosine phosphorylation. These results also raise the possibility that certain growth-promoting effects of Ca2+ -mobilizing agents such as angiotensin II may be mediated via tyrosine phosphorylation.
Mol Cell Biol 1990 Dec
PMID:Angiotensin II stimulates protein-tyrosine phosphorylation in a calcium-dependent manner. 170 Oct 16


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