Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The brain is one of the organs where an intrinsic renin-angiotensin system (RAS) has been described. Stimulation of circumventricular or brainstem angiotensin II (Ang II) receptors engenders a distinct pattern of cardiovascular, endocrine, and behavioral responses featuring blood pressure increase, attenuation of the baroreceptor reflex, drinking, release of pituitary hormones such as vasopressin, oxytocin, and ACTH, and natriuresis. In contrast to most of the other central actions of Ang II, the natriuretic effect cannot be elicited by Ang II as a circulating hormone. Recently, we have shown that stimulation of Ang II AT-1 receptors in the circumventricular organs causes a selective release of norepinephrine (NE) in the paraventricular nucleus (PVN) and in the supraoptic nucleus (SON). As vasopressin is also released from the PVN and SON, it is possible that the Ang II-NE interaction is involved in the release of vasopressin, thereby contributing to central blood pressure regulation and volume control. Finally, a substantial body of results suggests that an overactivity of the brain renin-angiotensin system is one of the contributors to genetic hypertension. However, this idea needs further confirmation.
J Cardiovasc Pharmacol 1992
PMID:Role of brain angiotensin in cardiovascular regulation. 138 68

Extracellular recordings were made from anteroventral third ventricle (AV3V) and supraoptic nucleus (SON) neurons of rat hypothalamus in slice preparations. ET-3 was applied at concentrations of 10(-10) to 3 x 10(-7) M. Of 119 AV3V neurons tested, 21 (18%) were excited, 8 (6%) were slightly inhibited, and 90 (76%) were unaffected. The threshold concentration to evoke responses was approximately 10(-8) M. Excitatory responses of the AV3V neurons to ET-3 remained in a Ca(2+)-free medium. Of 120 SON neurons tested, 46 were phasic (putative vasopressin neuron) and 74 were nonphasic (putative oxytocin neuron). Of 46 phasic neurons tested, 26 (56.5%) were inhibited by ET-3, 20 (43.5%) were nonresponsive, and none was excited. Of 74 nonphasic neurons tested, 14 (19%) neurons were inhibited by ET-3, 60 (81%) were nonresponsive, and none was excited. These results suggest that ET-3 has dual effects on AV3V and SON neurons and the mechanisms of the responses may be different in the AV3V and SON neurons.
J Cardiovasc Pharmacol 1991
PMID:Endothelin-3 directly affects neurons in the anteroventral third ventricle region and supraoptic nucleus of the rat hypothalamus in vitro. 172 32

Endothelin-3-like immunoreactivity (ET-3-ir) was detected in extracts of rat hypothalamic median eminence, and in the anterior and neurointermediate lobes of the pituitary at levels (ng ET-3/mg protein) exceeding those present in extracts of abdominal aorta. This ET-3-ir appeared authentic because radioimmunoassay (RIA) dose-response curves parallel to those of synthetic ET-3 could be constructed and this ET-3-ir comigrated on C-8 high-pressure liquid chromatography (HPLC) with synthetic ET-3. Endothelin-1-like immunoreactivity, on the other hand, was abundant in extracts of abdominal aorta and cerebral cortex and only minimally present in hypothalamus and anterior pituitary gland. Central administration of 11 and 23 pmol ET-3 resulted in significant (4.2- and 5.7-fold, respectively) elevations of plasma levels of vasopressin. Oxytocin levels were transiently, yet significantly, elevated (1.8-fold) by the higher dose of ET-3. These results, and our findings that central administration of ET-3 inhibits stimulated water drinking, suggest a physiologically important role for endogenously produced endothelin in the central mechanisms regulating fluid and electrolyte homeostasis.
J Cardiovasc Pharmacol 1991
PMID:Hypothalamic endothelin: presence and effects related to fluid and electrolyte homeostasis. 172 77

The nonapeptide vasopressin is synthetized as part of a longer common precursor polypeptide, together with its carrier protein neurophysin and a glycopeptide of unknown function. The gene for this common precursor has been isolated and sequenced and shown to comprise three exons encoding, respectively, the protein domains approximately corresponding to the N-terminal leader peptide and hormone, to most of the neurophysin, and to the glycopeptide. In the Brattleboro rat, the hereditary hypothalamic diabetes insipidus, characteristic of this strain, has been shown to be caused by a single nucleotide deletion in the vasopressin gene. This leads to the much reduced synthesis of a mutant vasopressin precursor, whose C terminus is quite unlike that in wild-type rats and which does not appear to be correctly processed in vivo.
J Cardiovasc Pharmacol 1986
PMID:Biosynthesis of vasopressin. 243 69

To investigate the role of arginine vasopressin (AVP) in genetic hypertension, we measured 24-h urinary volume, osmolality, and 24-h AVP excretion, as well as pituitary and pineal AVP and oxytocin levels, in genetically hypertensive (LH), normotensive (LN), and low blood pressure (LL) 5-and 45-week-old female rats of the Lyon strains. We also determined vascular sensitivity to AVP, norepinephrine, and angiotensin II in 6- and 21-week-old rats. AVP secretion was increased in both LH and LL rats compared with LN controls. Previous reports of increased AVP secretion in spontaneously hypertensive rats have suggested that AVP might play a role in high blood pressure. The existence of a similar increase in LL rats indicates that genetic hypertension of LH rats is not related directly to their increased AVP secretion. Furthermore, the vascular sensitivity to AVP was not specifically enhanced in 21-week-old LH rats compared with LN and LL controls. This study provides evidence against a major role of vasopressin in the genesis and maintenance of high blood pressure in this model of experimental hypertension, and emphasizes that the choice of controls in such investigations is of crucial importance.
J Cardiovasc Pharmacol
PMID:Vasopressin and oxytocin in genetically hypertensive rats of the Lyon strain. 619 19

Like endothelin-1 (ET-1), its immediate human precursor big ET-1 (1-100 nM) increased the rate of spontaneous phasic contractions and caused graded tonic contractions of isolated rat uterus strips. The tonic contraction to big ET-1 (10 nM) was markedly blocked by phosphoramidon (100 microM), which did not modify the response to an equipotent concentration of ET-1 (3 nM). Responses to big-ET-1 (30 nM) were abolished in calcium-free medium, but those to ET-1 (10 nM) were only reduced by this condition. The EC50 of big ET-1 for inducing tonic contraction was only sevenfold greater than that of ET-1, and both peptides produced a maximal response similar to that evoked by KCl 80 mM. ET-3 was much less potent. The selective ETA receptor antagonist BQ-123 (40-600 nM) caused graded rightward shifts of the ET-1 curve without affecting the maximal response, yielding a Schild plot with a slope not different from unity and a pA2 value of 7.76. BQ-123 (100 nM) did not affect contractions induced by oxytocin (5 nM), acetylcholine (3 microM), or bradykinin (0.3 nM), but inhibited responses to both big ET-1 and ET-1. Therefore, the rat uterus contains a phosphoramidon-sensitive, calcium-dependent endothelin-converting enzyme that readily converts big ET-1 into ET-1, which then contracts the myometrium via activation of ETA receptors.
J Cardiovasc Pharmacol 1993
PMID:Conversion of big endothelin-1 in rat uterus causes contraction mediated by ETA receptors. 750 42

To investigate how the effects of oxytocin on blood pressure are influenced by female sex hormones, oxytocin (1 mg/kg, s.c.) was given to intact cycling and ovariectomized (OVX) female rats. Oxytocin caused a transient increase in blood pressure, most pronounced during proestrus (p < 0.01) and estrus (p < 0.01). This increase was partially antagonized by an oxytocin antagonist. When oxytocin was given for 5 days, blood pressure decreased (intact rats: 123+/-1.5 vs. 130+/-1.3 mm Hg; p < 0.001, OVX rats: 120+/-3.0 vs. 129+/-1.1 mm Hg; p < 0.001). This decrease, not abolished by the oxytocin antagonist, persisted for 3 weeks in intact rats and for 8 days in OVX rats. If oxytocin treatment of OVX rats continued, a nadir of 12 mm Hg (118+/-1.7 mm Hg; p < 0.001) was reached after 8 days. Thereafter heart rate decreased significantly (p < 0.05). One daily oxytocin injection for 12 days to OVX rats decreased blood pressure for 3 weeks, as in intact rats. These results show that acute and chronic oxytocin treatment cause opposite effects on blood pressure, and that these effects are modified by female sex hormones.
J Cardiovasc Pharmacol 1999 Jan
PMID:Short-term increase and long-term decrease of blood pressure in response to oxytocin-potentiating effect of female steroid hormones. 989 Apr 3

In this paper, we review our current understanding of the medicinal chemistry of the major peptide systems, which influence body fluid homeostasis. Electrolytes play pivotal roles in intra- and intercellular communication, acid-base equilibrium and, when bound to several macromolecules, they regulate a myriad of enzymatic proteins, receptors and transcription factors. Cell turgor influences the plasma membrane, which activates mechanically-gated ion channels or mechanoreceptors, and the expression of a number of genes which underlie long-term metabolic responses to hormones, substrates and reactive oxygen intermediates. The altered kinetics and enzymatic cleavage of peptides during water-electrolyte imbalance can contribute to cardiac and renal damage associated with elevated blood pressure. Identification of the enzymes which are responsible for cleavage, together with emerging information about the mechanisms of action and structures of regulatory and effector peptides, has laid a foundation for the discovery of novel drugs, some of which are in use or are now undergoing evaluation in experimental trials. The development of models of hydrosaline challenge with relative efficiency to induce selective water-electrolyte imbalance has permitted the identification of kallikrein-kinin, renin-angiotensin-aldosterone, vasopressin-oxytocin, thyrotropin-releasing hormone and luteinizing hormone-releasing hormone as susceptible substrates. At present, the angiotensin-I converting enzyme inhibitors are well-known efficacious, orally active, blood pressure-lowering agents which have been used in hypertensive patients. In addition to several new analogues of this class of drug, some selective dual inhibitors of angiotensin-I converting enzyme and neutral endopeptidase and inhibitors of aminopeptidases are now also being rationally assayed and their beneficial effects on hypertension and hydromineral balance indicate that this type of drug may have powerful therapeutic effects for disorders of body fluid homeostasis.
Curr Med Chem Cardiovasc Hematol Agents 2004 Jul
PMID:Peptide metabolism and the control of body fluid homeostasis. 1532 Jul 88

Endothelin-1 (ET-1) in the central nervous system has been suggested to produce suppressive effects on pain transmission. We investigated the manner by which ET-1 exerts this action. ET-1 administered intracerebroventricularly produced a dose-dependent antinociceptive effect in a thermal pain test that utilized a spinal reflex to determine nociceptive thresholds. This suggested that the antinociceptive effect of ET-1 involved a descending pain inhibitory system. The antinociceptive effect was blocked by an ETA receptor antagonist but not by an ETB receptor antagonist, indicating that the action was mediated through the ETA receptor. Antagonists of opioid receptors, serotonin receptors, alpha-2 adrenergic receptors, oxytocin receptors, and dopamine receptors did not block the antinociceptive effect of ET-1. Thus, major descending inhibitory systems were probably not involved. The antinociceptive effect was blocked by intracerebroventricular administration of an alpha-1 adrenergic receptor antagonist. This indicated that the antinociceptive effect involved the activation of a supraspinal noradrenergic pathway, which in turn may activate a still unknown descending pain inhibitory system.
J Cardiovasc Pharmacol 2004 Nov
PMID:Inhibitory actions of endothelin-1 on pain processing. 1583 10

Dopamine receptors have been identified in a number of organs and tissues, which include the central and peripheral nervous systems, various vascular beds, the heart, the gastrointestinal tract, and the kidney. Dopamine receptors are classified into D1- and D2- like subtypes based on their structure and pharmacology; during conditions of moderate sodium balance, more than 50% of renal sodium excretion is regulated by D1-like receptors. Most of the knowledge on the actions of dopamine has been focused on the D1 dopamine receptor. The D5 dopamine receptor also belongs to the D1- like receptor subfamily. Disruption of the D5 receptor results in hypertension. However, unlike the D1 receptor, the hypertension in D5 receptor null mice is caused by the increased activity of the sympathetic nervous system, apparently due to activation of oxytocin, V1 vasopressin, and non-NMDA receptors in the central nervous system. In this paper, we review the physiological action of D5 receptor on the central and peripheral nervous systems, and discuss the possible mechanisms by which hypertension develops when the D5 receptor function is perturbed.
Cardiovasc Hematol Agents Med Chem 2007 Jul
PMID:Regulation of blood pressure by D5 dopamine receptors. 1763 Sep 51


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