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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Experimental studies relating to the direct peripheral vascular actions of neurohypophyseal hormones and their synthetic variants are reviewed. In addition, the available data on the comparative pharmacologic actions of these peptides on mammalian vascular smooth muscle are reviewed. Experiments relating to mechanisms by which neurohypophyseal peptides induce contraction of blood vessels are discussed. Neurohypophyseal peptide hormones appear to be able to contract and relax vascular smooth muscle, the exact type of response being dependent on species, vascular bed, and region within a vascular bed. Receptors that subserve both contraction and relaxation may exist on different blood vessels within a species, with a preponderance of receptors that subserve contraction being present in most blood vessels. Concentrations of vasopressin that can be considered physiologic (i.e., 10(-13) to 10(-11) M) are capable of evoking responses on a variety of microscopic as well as large blood vessels. Arginine-vasopressin appears to be, relatively, the most potent contractile substance on rat blood vessels investigated to date; angiotensin is not. Preservative-free oxytocin is a contractile agent on all mammalian arterial and arteriolar vessels so far investigated. A great deal of the controversy surrounding the exact vascular actions elicited by these peptide hormones can be attributed to many factors that were not controlled in older experiments. Moreover, rat pressor assays cannot be utilized to determine structure-activity relationship for neurohypophyseal peptides on vascular smooth muscles. Nuerohypophyseal peptide-induced contractions of vascular smooth muscles can be markedly affected by sex, sex hormones, alcohols, [Ca2+]0, [mg2+]0, oxygen deficit, and glucose-deprivation. Extracellular sodium and potassium ions appear to play relatively little role in vasopressin-induced contractions of rat arterial smooth muscle. The terminal amino group, phenolic hydroxyl, aromatic ring and basicity in positions 1, 2, 3, and 8, respectively, of the neurohypophyseal hormones are important for optimizing hormone-receptor affinity and intrinsic contractile activity on vascular smooth muscle. Basicity in position 8 of these peptide hormones is not an absolute requirement for contractile activation of these smooth muscles. Alterations in molecular structure can result in neurohypophyseal peptides with unique, and selective, microcirculatory effects that may be beneficial in the treatment of low-flow states.
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PMID:Vascular smooth muscle and neurohypophyseal hormones. 32 65

Myometrial tissue was obtained from non-pregnant women subjected to hysterectomy because of various gynaecological disorders, and from women undergoing caesarean section. Strip preparations were dissected and isometric tension was recorded. Nifedipine (2.9 X 10(-8)--2.9 X 10(-6)M) inhibited spontaneous contractile activity, mainly by reducing the amplitude of contraction in both non-pregnant and pregnant myometrium. The drug also inhibited potassium induced contractions in a concentration dependent manner. This effect seemed to be more pronounced in pregnant than in non-pregnant tissue. In preparations of pregnant human myometrium, normally polarized or potassium depolarized, oxytocin induced a contractile activity that was effectively inhibited by nifedipine. Nifedipine also relaxed contractions induced by vasopressin in isolated non-pregnant myometrium. It is concluded that the relaxant effect of nifedipine on isolated pregnant and non-pregnant human myometrium can be explained by inhibition of calcium influx. The results thus support the view, that calcium influx is an important step in the initiation of contractile activity in human uterine smooth muscle.
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PMID:Relaxant effects of nifedipine on isolated, human myometrium. 49 17

Intra-arterial injections of bradykinin into the hindlimb of the rabbit cause two types of cardiovascular reflex effects displayed in succession. The first-type effects appear early and are of inhibitory nature, being represented by systemic hypotension, contralateral hindlimb vasodilation and bradycardia; the second-type effects appear later and are excitatory in nature, consisting of hypertension, hindlimb vasoconstriction and tachycardia and occur closely associated with behavioral manifestations typical of the reaction to pain. Both the depressor and pressor effects are accompanied by hyperventilation. Analogous biphasic reflex responses may be caused by intraarterial injections of potassium ions. On the contrary, hypertonic solutions (NaCl, glucose) usually only produce second-type excitatory responses. No significant cardiocirculatory reflex effects are induced by even high doses of serotonin, nicotine, adenosine, adenosine triphosphate, adrenalin, noradrenalin, angiotensin, vasopressin and oxytocin. General anesthesia greatly inhibits the pressor reflexes and potentiates the depressor responses (to bradykinin and K ions) but does not appear to be a necessary condition for provoking depressor reflexes by chemical stimulation of somatic afferents. Both chemoreflex responses are prevented by sectioning the somatic nerves of the injected limb. Denervation of sinoaortic areas and of cardiopulmonary receptors by bilateral cervical vagotomy or complete removal of the skin from the injected limb does not prevent either type of chemoreflex response. These depressor and pressor chemoreflexes have been ascribed to activation of two functionally distinct types of sensory receptors in the skeletal muscle, differently sensitive to chemical substances and selectively concerned with different patterns of cardiocirculatory reflex response.
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PMID:Cardiovascular and respiratory chemoreflexes from the hindlimb sensory receptors evoked by intra-arterial injection of bradykinin and other chemical agents in the rabbit. 76 67

35S-cysteine injected adjacent to the supraoptic nucleus (SON) of the rat is rapidly incorporated into proteins. These 35S-cysteine-labeled proteins in the SON (1-24 h after injection) were separated by polyacrylamide gel electrophoresis, and the distribution of radioactive proteins on the gels was analyzed. 1 h after injection, about 73% of the radioactivity appeared in two peaks (both about 20,000 mol wt). With time, these peaks (putative precursors of neurophysin) decreased, as a 12,000 mol wt peak (containing two distinct neurophysins) increased in radioactivity. Both the 20,000- and 12,000-mol wt proteins are transported into the axonal (median eminence) and nerve terminal (posterior pituitary) regions of the rat hypothalamo-neurohypophysial system. Conversion of the larger precursor protein to the smaller neurophysin appears to occur, in large part, intra-axonally during axonal transport. Six distinct 35S-cysteine-labeled peptides (less than 2500 mol wt), in addition to arginine vasopressin and oxytocin, are also synthesized in the SON and transported to the posterior pituitary where they are released together with labeled neurophysin by potassium depolarization in the presence of extracellular calcium. These data provide support for the hypothesis that the neurohypophysial peptides (vasopressin and oxytocin) and neurophysins are derived from the post-translational clevage of protein precursors synthesized in the SON, and that the conversion process can occur in the neurosecretory granule during axonal transport.
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PMID:Biosynthesis and axonal transport of rat neurohypophysial proteins and peptides. 85 41

Cytochemical methods using silver proteinate, silver methenamine an potassium ferrocyanide + OsO4 for ultrastructural detection of glycoproteins allow, in the posthypophysis and the magnocellular nuclei of the rat, differentiation of two types of fibres and neurons: one type containing negative granules with a homogenous content of low electron density, the second type containing granules which demonstrate a ring shaped deposit either of silver or of potassium ferrocyanide-osmium complex, likely to be related to a glycoprotein component. The difference between these two types is increased by prestaining "en bloc" with uranyl acetate before the silver proteinate reaction. A similar investigation was carried out on the vasopressin deficient Brattleboro rat; the neurosecretory material, present in some endings and neurons only, is of the nonreactive type, so that it appears justified to correlate the reactivity of granules with vasopressin, consequently to distinguish neurones and fibres containing vasopressin from those in which oxytocin is quantitatively the main hormonal peptide. This conclusion is strongly supported by the fact that percentages of reactive and negative endings, as determined on this basis in the posthypophysis of normal rats from two different strains, are in good agreement with biochemical data reported in the literature.
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PMID:Cytochemical duality of neurosecretory material in the hypothalamo-posthypophysial system of the rat as related to hormonal content. 87 84

The available evidence suggests that hormones and neurophysins are associated exclusively with the neurosecretory granules, each of which contains approximately 6 times 10-4 molecules of each. Hormones and carrier proteins are complexed within the granules and the complexes are densely packed. The processes that keep the intragranular space in osmotic equilibrium with the axoplasm require further study. Freeze-fracture data, as well as studies in which histochemical methods for the detection of glycoproteins were used, suggest that the intragranular aspect of the granule membrane mostly resembles the extracellular half of the plasma membrane; on the other hand, the cytoplasmic aspects of plasma and granule membrane have similar characteristics, which may be important in permitting membrane fusion to take place prior to secretion. Little is known about the molecular species involved in this interaction between granule and plasma membrane, except that calcium is a cofactor in this process. Release is triggered in vivo by propagated action potentials which cause an influx of calcium into the secretory endings. Newly formed granules, and other granules located at the periphery of the endings are preferentially released. Irrespective of the type of stimulation of secretion, release involves the diffusion into the extracellular space of granule core constituents. The best evidence so far in support of this view comes from ultrastructural studies showing images of exocytosis, as well as from biochemical studies demonstrating that hormones and carrier proteins are secreted concomitantly in a great variety of experimental or clinical conditions, without an associated release of granule membrane constituents or of enzymes of cytoplasmic origin. Recovery mechanisms following secretion require new synthesis of granule constituents and restoration of the resting internal concentrations of potassium, sodium, and calcium. Membrane surface area is restored following exocytosis by compensatory endocytosis which involves indiscriminate uptake of extracellular medium into the secretory axon terminals. While much progress has been made in research on the cellular and subcellular processes that take place in neurons which produce, store, and secrete neurohypophyseal hormones and their carrier proteins, neurophysins, many pressing questions remain to be answered. New developments, such as organ culture of supraoptic nuclei94-96 and the recent isolation of a clone of mouse hypothalamic cells capable of synthesizing vasopressin and neurophysin,97 will hopefully allow some of these problems to be solved in the future.
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PMID:A review on neurosecretory granules: their contents and mechanisms of release. 109 Nov 94

Isolated rat neural lobes were incubated in vitro in Locke's solution containing anaesthetic quantities of urethane, pentobarbitone or tribromoethanol. The oxytocin content of the incubation medium was estimated before, during and after stimulation of the tissue by raising the potassium chloride concentration from 5-6 to 56 mmol/l. Urethane (25 mmol/l) significantly potentiated oxytocin release (P less than 0-01) whereas tribromoethanol (0-5 mmol/l) had no obvious effect and pentobarbitone (0-4 mmol/l) significantly (P less than 0-01) inhibited its release. Reduction of the sodium chloride concentration in the medium potentiated the release of oxytocin in each case but did not alter its pattern. Urethane which increased secretion of oxytocin also increased calcium ion uptake by the neural lobes and pentobarbitone which decreased oxytocin release decreased calcium ion uptake. The results may explain why the blood concentration of the neurohypophysial hormones tends to be higher in rats anaesthetized with urethane than with tribromoethanol. Inhibition of hormone release by pentobarbitone suggests that this anaesthetic is unsuitable for use in studies of neurohypophysial hormone release. A partial explanation of the anaesthetic properties of urethane and pentobarbitone may also have been found if the release of neurotransmitter substances is influenced in a similar manner.
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PMID:Potentiation by urethane and inhibition by pentobarbitone of oxytocin release in vitro. 110 67

Seventy-four patients, from 16 to 20 weeks pregnant, received intra-amniotic urea (80 Gm.) and intravenous oxytocin for the purpose of inducing abortion. Seventy-one of the 74 patients were successfully aborted by the primary method with a mean injection-to-abortion interval of 18.33 hours. There were no serious side effects, and the mean hospital stay was 32 hours. Following urea injection, the mean serum urea nitrogen rose to 33 mg. per cent at 4 hours. Maximum changes in serum electrolytes occurred at 8 to 12 hours after injection and included a decrease in the mean concentrations of sodium, chloride, and carbon dioxide and an increase in serum potassium. An increase in the urinary excretion of urea began within 4 hours, but significant diuresis did not occur in the presence of intravenous oxytocin administration. There was a significant increase in the leukocyte concentration while hematocrit values remained unchanged. Beginning approximately 8 hours following urea injection, the mean plasma fibinogen concentrations decreased by approximately 15 per cent and the mean platelet count showed a drop of approximately 18 per cent. Fibrinogen-fibrin degradation products were significantly increased in 36 per cent of the patients studied.
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PMID:Intra-amniotic urea as a midtrimester abortifacient: clinical results and serum and urinary changes. 111 18

The efflux of [3-H]GABA from glial cells in the rat posterior pituitary was followed in isolated glands incubated in the presence of 10-minus 5 M aminooxyacetic acid which is known to inhibit GABA metabolism. Electrical stimulation of the pituitary stalk evoked an increase in the rate of efflux of [3-H]GABA as did elevation of the extracellular potassium concentration. The release of neurophysin from nerve terminals in the gland was also increased by electrical stimulation. The increase in [3-H]GABA efflux appeared to be independent of frequency at 2, 5, or 25 HZ if the number of pulses delivered was kept constant, although stimulation at 10 HZ was more effective than either 2 or 25 HZ. The efflux of [3-H]GABA evoked by 56 mM K+ was inhibited by 50% when calcium was removed from the washing fluid and 3 mM EGTA added, while the response evoked by electrical stimulation was unaffected by this procedure. The electrically induced efflux of [3-H]GABA was inhibited by 50% when choline chloride was substituted for sodium chloride in the washing medium, although it was unaffected by tetrodotoxin (0.8 times 10-minus 6 g/ml). The release of exogenous GABA from the pituicyte glia is compared with that of neurophysin from the nerve terminals in the posterior pituitary, and the results are discussed with reference to possible mechanisms of the glial release process.
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PMID:The release of [3-H]gamma-aminobutyric acid and neurophysin from the isolated rat posterior pituitary. 113 91

1. Membrane potentials have been recorded from cells of seminiferous tubules of rats in vitro using micro-electrodes. The value in 808 impalements was -28-2 +/- 0-3 mV (mean +/- S.E.) at 33 degrees C. 2. Increasing the potassium concentration depolarized the cells, a tenfold increase in concentration causing a depolarization of 16 mV. Removal of sodium from the bathing solution caused a hyperpolarization of 3 mV at a potassium concentration of 5-9 m-equiv/l. Removal of chloride and replacement with impermeant anions had no effect on potential. Removal of calcium from the bathing solution caused a minor but significant depolarization. 3. Ouabain (10-3 M), dinitrophenol (2-5 times 10-4 M) or removal of glucose from the bathing fluid all caused depolarization. The membrane potentials of the cells were sensitive to temperature over the range 10-33 degrees C, the apparent activation energy for the reactions maintaining the potential being approximately 6 kcal/mole. 4. Membrane potentials in seminiferous tubules were independent of age of the animal, were insensitive to previous hypophysectomy and were insensitive to a number of hormones (FSH, LH, HCG, oxytocin). In high concentration prostaglandin E1 caused depolarization. 5. Acetazoleamide (4 times 10-5 M) caused a rapid, but reversible, depolarization of the tubular cells. This was also true in conditions when the HCO'3/CO2 buffer system was replaced with Tris-buffer. Another carbonic anhydrase inhibitor (p-sulphonamido-benzoic acid) had similar effects on cell potentials as acetazoleamide. These results are discussed in relation to the nature of the ionic secretion produced in the tubules. 6. Occasional cells showed phasic variations in membrane potential. A possible connexion between these variations and the contractile activity of the tubules is discussed.
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PMID:Intracellular potentials in cells of the seminiferous tubules of rats. 115 7


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