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)

To determine if harmala alkaloids affect transport systems other than (Na +K)-ATPase, effects of harmaline on Na and water fluxes were studied in amphibian skins. Net Na flux was evaluated from short-circuit current, and water flux monitored with automatic, volumetric methods. At 2 to 5 mM, harmaline consistently inhibited SCC and prevented the natriferic effects of oxytocin and norepinephrine. However, at 0.1 to 0.5 mM, harmaline produced an increase in SCC inhibitable with amiloride. The stimulatory effects of harmaline and oxytocin were either nonadditive or additive depending on whether the hallucinogen was present in the inner solution or in the outer solution bathing the skin, respectively. Water flow was not modified by harmaline on the outer medium. In contrast, addition of the drug to the inner medium elicited a conspicuous, sustained, vasopressin-like, hydrosmotic effect, comparable to and competive with those of vasopressin and norepinephrine. The ensemble of these results suggests that harmaline may affect three distinct transport systems: (i) the Na pump; (ii) the cyclic nucleotide system; (iii) the Na entry pathway at the outer membrane of the skin that is also activated by agents such as diphenylhydantoin, lanthanides and propranolol.
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PMID:Vasopressin-like effects of a hallucinogenic drug--harmaline--on sodium and water transport. 41 80

We have compared the response of proton and water transport to oxytocin treatment in isolated frog skin and urinary bladder epithelia to provide further insights into the nature of water flow and H+ flux across individual apical and basolateral cell membranes. In isolated spontaneous sodium-transporting frog skin epithelia, lowering the pH of the apical solution from 7.4 to 6.4, 5.5, or 4.5 produced a fall in pHi in principal cells which was completely blocked by amiloride (50 microM), indicating that apical Na+ channels are permeable to protons. When sodium transport was blocked by amiloride, the H+ permeability of the apical membranes of principal cells was negligible but increased dramatically after treatment with antidiuretic hormone (ADH). In the latter condition, lowering the pH of the apical solution caused a voltage-dependent intracellular acidification, accompanied by membrane depolarization, and an increase in membrane conductance and transepithelial current. These effects were inhibited by adding Hg2+ (100 microM) or dicyclohexylcarbodiimide (DCCD, 10(-5) M) to the apical bath. Net titratable H+ flux across frog skin was increased from 30 +/- 8 to 115 +/- 18 neq.h-1.cm-2 (n = 8) after oxytocin treatment (at apical pH 5.5 and serosal pH 7.4) and was completely inhibited by DCCD (10(-5) M). The basolateral membranes of the principal cells in frog skin epithelium were found to be spontaneously permeable to H+ and passive electrogenic H+ transport across this membrane was not affected by oxytocin. Lowering the pH of the basolateral bathing solution (pHb) produced an intracellular acidification and membrane depolarization (and an increase in conductance when the normal dominant K+ conductance of this membrane was abolished by Ba2+ 1 mM). These effects of low pHb were blocked by micromolar concentrations of heavy metals (Zn2+, Ni2+, Co2+, Cd2+, and Hg2+). Lowering pHb in the presence of oxytocin (50 mU/ml) produced a transepithelial current (3 microA.cm-2 at pHb 5.5) which was blocked by 100 microM of Hg2+, Zn2+, or Ni2+ at the basolateral side, and by DCCD (10(-5) M) or Hg2+ (100 microM) from the apical side. The net hydroosmotic water flux (JH2O) induced by oxytocin in frog bladder sacs was blocked by inhibitors of H(+)-adenosine triphosphatase (ATPase). Diethylstilbestrol (DES 10(-5) M), oligomycin (10(-8) M), and DCCD (10(-5) M) prevented JH2O when present in the lumen. These effects cannot be attributed to inhibition of metabolism since cyanide (10(-4) M), or 2-deoxyglucose (10(-3) M) had no effect on JH2O.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Common channels for water and protons at apical and basolateral cell membranes of frog skin and urinary bladder epithelia. Effects of oxytocin, heavy metals, and inhibitors of H(+)-adenosine triphosphatase. 164 38

Activity-dependent modulation of excitable responses from neurohypophysial axons and their secretory swellings has long been recognized as an important regulator of arginine vasopressin and oxytocin release during patterned stimulation. Various activity-dependent mechanisms, including action potential broadening, potassium accumulation, and autocrine or paracrine feedback, have been proposed as underlying mechanisms. However, the relevance of any specific mechanism on net excitability in the intact preparation, during different levels of overall activation, and during realistic stimulation with trains of action potentials has remained largely undetermined. Using high-speed optical recordings and potentiometric dyes, we have quantified the dynamics of global excitability under physiologically more realistic conditions, that is in the intact neurohypophysis during trains of stimuli at varying frequencies and levels of overall activity. Net excitability facilitated during stimulation at low frequencies or at low activity. During persistent high-intensity or high-frequency stimulation, net excitability became severely depressed. Depression of excitable responses was strongly affected by manipulations of extracellular potassium levels, including changes to resting [K(+)](out), increases of interstitial spaces with hypertonic solutions and inhibition of Na(+)/K(+) ATPase activity. Application of the GABA(A) receptor blocker bicuculline or manipulations of Ca(2+) influx showed little effect. Numerical simulation of K(+) accumulation on action potentials of individual axons reproduced optically recorded population responses, including the overall depression of action potential (AP) amplitudes, modest AP broadening and the prominent loss of hyperpolarizing undershoots. Hence, extracellular potassium accumulation dominates activity-dependent depression of neurohypophysial excitability under elevated stimulation conditions. The intricate dependence on the short-term stimulation history and its resulting feedback on neurohypophysial excitability renders [K(+)](out) accumulation a surprisingly complex mechanism for regulating axonal excitability and subsequent neuroendocrine release.
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PMID:Potassium accumulation as dynamic modulator of neurohypophysial excitability. 2043 4