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

Cells having morphological and histochemical properties of collecting tubules were isolated from rabbit renal papillae. Confluent monolayer cultures of these renal papillary collecting tubule (RPCT) cells formed hemicysts and adhered with morphological asymmetry to Millipore filters. Cultures of 1-day-old RPCT cells synthesized cAMP in response to arginine vasopressin (AVP) (half-maximal response to 10(-10) M), oxytocin, and parathyroid hormone (half-maximal responses at 5 X 10(-9) M) but not to adrenergic agents. After 10 days of growth (fourfold increase in cell number) RPCT cells retained the same pattern of histochemical and hormonal responses as 1-day-old cells. Hormones were tested for their influence on the release of immunoreactive prostaglandins (iPG) by RPCT cells; the major product under both basal and stimulated conditions was iPGE2. At very low concentrations (greater than or equal to 10(-10) M), bradykinin, lysyl-bradykinin, and methionyl-lysyl-bradykinin caused four- to sixfold increases in the rate of iPGE2 formation within 3 min; smaller (less than twofold) increases were observed with relatively high concentrations of epinephrine (10(-5) M), norepinephrine (10(-5) M), and angiotensin II (10(-7) M), but only after longer incubations. Significantly, neither AVP (10(-7) M) nor [deamino]AVP (10(-7) M) caused prostaglandin release by RPCT cells. Our results indicate that kinins can act directly on the collecting tubule to elicit PGE2 formation; furthermore, this effect of kinins may be natriuretic, since PGE2 has been shown to inhibit Na+ resorption by the medullary collecting tubule and thick ascending limb.
 ...
PMID:Kinin-induced prostaglandin synthesis by renal papillary collecting tubule cells in culture. 626 8

Synthetic bovine parathyroid hormone containing the NH2 terminal 34 amino acids [bPTH-(1-34)] was recently demonstrated to inhibit oxytocin stimulated uterine contraction in vitro. The parathyroid hormone analogues [Nle8, Nle18, Tyr34]bPTH-(3-34)amide [NTA-(3-34)] and [Tyr34]bPTH-(7-34)amide [NTA-(7-34)] have been reported to act as inhibitors of antagonists of parathyroid hormone (PTH) in numerous assays. In the present study the effects of these PTH analogues on uterine contraction and the ability of these analogues to act as antagonists to the uterine inhibitory action of bPTH-(1-34) in vitro were investigated. The NTA-(3-34) fragment had no effect on oxytocin stimulated uterine contractions. However, the NTA-(3-34) fragment was able to alter the ability of bPTH (1-34) to reduce oxytocin stimulated uterine contraction in a dose-related manner. Bovine PTH(1-34) (0.3 microgram/ml) reduced the contractile response obtained with oxytocin (0.5 mU/ml) by 20%. A dose of 15 micrograms/ml) of NTA-(3-34) abolished this inhibitory action of bPTH-(1-34) on oxytocin stimulated uterine contraction. In contrast the NTA-(7-34) caused a change in itself, stimulated contraction of resting uterine horns in a dose-related manner; 3.0 micrograms/ml of NTA-(7-34) caused a change in gram tension of + 1.5 grams. Bovine PTH-(1-34) was able to reduce the uterine contraction stimulated by NTA-(7-34) and 0.3 microgram/ml of bPTH-(1-34) reduced the contractile response obtained with 3.0 micrograms/ml of NTA-(7-34) by as much as 70%.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Effects of bPTH fragments (1-34), (3-34) and (7-34) on uterine contraction. 647 69

A number of previous investigations have indicated that the pituitary may directly stimulate secretion of parathyroid hormone. Others have disagreed. With the recent development of an in vitro bovine parathyroid perfusion system, the direct effect of suspected secretagogues can be assessed on a dynamic, ongoing basis. A partially purified pituitary extract (preparation A) was injected into calves. The plasma calcium increased an average of 1.1 mg/100 ml plasma. No increase of immunoreactive parathyroid hormone (iPTH) was detected, however, in the peripheral plasma prior to the increase in plasma calcium concentration. Since the peripheral plasma iPTH concentration has been shown to be relatively insensitive to changes in the secretion rate, the inability to detect a change in the iPTH concentration does not preclude a direct stimulating effect of the pituitary on the parathyroid. When preparation A was tested on in vitro perfused bovine parathyroid glands, a 30% average increase in secretion of c-iPTH (carboxy terminus) and a 56% average increase in secretion of n-iPTH (amino terminus) was observed under normocalcemic conditions. Under conditions of hypercalcemia, there was an average increase in the c-iPTH secretion rate of 60% and an average n-iPTH secretion rate increase of 88%. A failure of TSH, LH, GH, ADH, oxytocin, and prolactin to stimulate iPTH was observed. Previous reports have eliminated ACTH, MSH, and lipotropin as possible parathyroid secretagogues. The concept of a parathyroid stimulating hormone (PTSH) located in the pituitary that can directly stimulate the parathyroid gland to secrete parathyroid hormone is consistent with the results of this investigation.
 ...
PMID:Pituitary stimulation of parathyroid hormone secretion: evidence in cattle for a parathyroid stimulating hormone. 742 44

Antidiuretic hormone and parathyroid hormone (PTH) inhibit HCO3- absorption by the rat medullary thick ascending limb (MTAL). Studies were performed on rat MTAL tubule suspension to specify the H(+)-HCO3- membrane transporters affected by these hormones and the implicated intracellular second messengers. Arginine vasopressin (AVP) and PTH stimulated cell adenosine 3',5'-cyclic monophosphate (cAMP) production with a relative rank order potency of AVP > rat PTH-(1-34) > bovine PTH-(1-84). Significant cell acidification in HCO3- -CO2-free medium, monitored in 2'7'-bis(carboxyethyl)-5(6')-carboxyfluorescein-loaded cells, was caused by 0.1 nM AVP, 1 nM rat PTH-(1-34), but not by < 100 nM bovine PTH-(1-84), as well as by 10(-4) M 8-bromo-cAMP and 2 x 10(-5) M forskolin; 10 nM AVP or rat PTH-(1-34) did not alter the intracellular pH when Na+/H+ antiport was inhibited by 2 mM amiloride. Prostaglandin E2 (PGE2, 10(-6) M), which inhibited AVP-stimulated cell cAMP production, reduced by 35% the cell acidification response to 10 nM AVP. AVP and 8-bromo-cAMP inhibited Na+/H+ antiport-dependent cell pH recovery from intracellular acidification, which was explained by a decrease in the Vmax of the antiporter. AVP did not directly affect K(+)-HCO3- cotransport and plasma membrane H(+)-ATPase of rat MTAL cells. Cytosolic calcium ([Ca2+]i), monitored in fura-2-loaded cells, was unaffected by up to 1 nM AVP, 100 nM PTH, glucagon, calcitonin, and oxytocin, and 1 microM PGE2; however, 100 nM AVP, but not 1-desamino-8-D-AVP (dDAVP), caused a peak increase in [Ca2+]i, even in the absence of extracellular Ca2+, and stimulated cell accumulation of [3H]inositol phosphates.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:cAMP-dependent control of Na+/H+ antiport by AVP, PTH, and PGE2 in rat medullary thick ascending limb cells. 838 52

Endothelins (ETs) were initially thought to be primarily involved in the control of cardiovascular activity, but the presence of ETs and their receptors in a wide variety of other tissues has suggested a much broader range of functions. Specific receptors for ETs are found in nonvascular tissues including neuronal, neuroendocrine, and endocrine cells. In addition, immunoreactive ETs are present in the brain, pituitary, and peripheral endocrine tissues. However, the ET levels in hypothalamo-hypophysial portal and peripheral blood are low, suggesting that the ET system participates in neuroendocrine regulation through paracrine and/or autocrine mechanisms. Both ETA and ETB receptors are expressed in the hypothalamus, adrenal, parathyroid glands, pancreas, ovary, uterus, placenta, and prostate, while only ETA receptors are expressed in GT1 neurons, anterior pituitary cells, alpha T3-1 immortalized gonadotropes, parathyroid-derived cells, thyrocytes, testicular Leydig and Sertoli cells, normal and neoplastic ovarian granulosa cells, chondrocytes, and other cell types. Activation of ET receptors elicits the sequence of cellular events typical of Ca(2+)-mobilizing receptors, with prominent increases in phosphoinositide hydrolysis and elevations of [Ca2+]i that occur in oscillatory and nonoscillatory modes depending on the cell type. ET-induced activation of the phosphoinositide/Ca(2+)- mobilizing pathway in neuronal and endocrine cells is associated with rapid stimulation of secretory responses, including release of gonadotropin-releasing hormone, oxytocin, vasopressin, substance P, atrial natriuretic peptides, gonadotropins, thyrotropin, growth hormone, parathyroid hormone, aldosterone, and catecholamines. On the other hand, ET has inhibitory actions on prolactin, progesterone, and renin release. In addition to stimulating phospholipase C-dependent pathways, ETs also activate phospholipase D-and MAP-kinase-dependent pathways in some of their target cells, as well as expression of early response genes and increased mitogenic activity. In many neuroendocrine cells, ET induces rapid and marked desensitization of its signaling system, in association with extensive internalization of ET receptors and reduced signaling and secretory responses. These findings raise the possibility that ETs participate in the control of secretory responses in the hypothalamo-pituitary system and peripheral endocrine cells, as well as in long-term aspects of regulation in certain neuroendocrine cells.
 ...
PMID:Expression and signal transduction pathways of endothelin receptors in neuroendocrine cells. 881 99

Under physiological conditions, maintenance of skeletal mass is the result of a tightly coupled process of bone formation and bone resorption. Disease states, osteoporosis included, arise when this delicate balance is disrupted such as in menopause, when estrogen levels decrease dramatically corresponding with the cessation of ovarian function. Current therapies for the treatment of osteoporosis, including estrogen replacement therapy, selective estrogen receptor modulators and bisphosphonates, are primarily based on blunting the resorption component of bone homeostasis. Although selective estrogen receptor modulators offer bone protection without the side effects of estrogen replacement therapy, there are some areas of improvement for the current generation of selective estrogen receptor modulators; particularly in reducing their antagonistic properties in the central nervous system that lead to vasomotor symptoms. There are few therapies that are focused on increasing bone formation, but they offer promising avenues in which to expand the repertoire of drugs to restore bone mass. Selective androgen receptor modulators, parathyroid hormone analogs, oxytocin analogs and statins, all with improved pharmacological properties in bone, are among the potential approaches to eliciting anabolic effects in the skeleton.
 ...
PMID:New approaches to the treatment of osteoporosis. 1095 65

Sex and the endocrine system exert a significant influence on the physiology and pathophysiology of the lacrimal gland. The purpose of this article is to briefly review the nature and magnitude of these interactions between sex, hormones and lacrimal tissue, and to address how they may relate to the pathogenesis of aqueous-deficient dry eye. Towards this end, this article has a 3-fold approach: first, to summarize the influence of androgens, estrogens, glucocorticoids, mineralocorticoids, retinoic acid, prolactin, alpha-melanocyte stimulating hormone, adrenocorticotropic hormone, luteinizing hormone, follicle-stimulating hormone, growth hormone, thyroid-stimulating hormone, arginine vasopressin, oxytocin, thyroxine, parathyroid hormone, insulin, glucagon, melatonin, human chorionic gonadotropin and cholecystokinin on the structure and function of the lacrimal gland; second, to discuss the mechanism of action of each hormone on lacrimal tissue; and third, to discuss the clinical relevance of the endocrine-lacrimal gland interrelationship, with a particular focus on each hormone's role (i.e. if relevant) in the development of aqueous-tear deficiency.
 ...
PMID:Tearful relationships? Sex, hormones, the lacrimal gland, and aqueous-deficient dry eye. 1721 82

Despite the high prevalence of primary uterine inertia in whelping bitches, the underlying pathogenesis remains unclear. The objectives were to i) determine serum concentrations of total calcium, ionized calcium (iCa), parathyroid hormone (PTH), and blood pH in normally whelping bitches throughout the peri-parturient period; and ii) investigate relationships among iCa, PTH, and acid-base status, and the role that they and oxytocin may have in the underlying pathogenesis of canine uterine inertia. Bitches were randomly selected from a population of German Shepherd Dog bitches with a history of uncomplicated parturition (Group 1; n=10), and from a population of Labrador bitches with a clinical history of an increased incidence of uterine inertia and stillbirths (Group 2; n=20). Jugular blood samples were collected daily from -4 d to the onset of whelping (t=0 h), and then every 4h until the last pup was born. Overall, bitches from Group 2 had higher mean+/-SEM serum concentrations of PTH (4.72+/-2.45 pmol/L, P<0.001), lower iCa (1.31+/-0.08 pmol/L, P<0.05), and higher venous pH (7.41+/-0.03, P<0.005) than bitches from Group 1 (2.9+/-1.44 pmol/L, 1.38+/-0.06 mmol/L, and 7.33+/-0.02, respectively) during the periparturient period. However, there was no significant difference between Groups 1 and 2 for serum oxytocin concentrations during the periparturient period (45.5+/-40 and 65.5+/-82 pg/mL). We inferred that low iCa resulting from a rising pH and decreasing PTH during the periparturient period may have contributed to decreased uterine contractility and increased risk of stillbirths. Therefore, manipulating the cationic/anionic difference in diets of pregnant bitches, similar to the bovine model for hypocalcamia, may reduce the incidence of stillbirths in the bitch.
 ...
PMID:Calcium, parathyroid hormone, oxytocin and pH profiles in the whelping bitch. 2017 20

Oxidation is a common degradation pathway that affects therapeutic proteins and peptides during production, purification, formulation, transportation, storage and handling of solid and liquid preparations. In the present work we review the scientific literature about structural and biological consequences of protein/peptide oxidation. Representative examples are discussed of specific products whose oxidation has been recently studied, including monoclonal antibodies, calcitonin, granulocyte colony-stimulating factor, growth hormone, insulin, interferon alpha and beta, oxytocin and parathyroid hormone. These examples illustrate that oxidation often leads to modifications of higher-order structures, including aggregate induction, and can generate products that are pharmacokinetically different, biologically less active and/or potentially more immunogenic than their native counterpart. It is therefore crucially important during the pharmaceutical development of therapeutic proteins and peptides to comprehensively characterize oxidation products and evaluate the impact of oxidation-induced structural modifications on the biological properties of the drug.
...
PMID:Oxidation of therapeutic proteins and peptides: structural and biological consequences. 2406 93


<< Previous 1 2