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

Although there is considerable evidence that depolarization of nerve cell terminals leads to the entry of Ca2+ and to the secretion of neurohormones and neurotransmitters, the details of how ionic currents control the release of neuroactive substances from nerve terminals are unknown. The small size of most nerve terminals has precluded direct analysis of membrane ionic currents and their influence on secretion. We now report that it is possible, using patch-clamp techniques, to study stimulus--secretion coupling in isolated peptidergic nerve terminals. Sinus gland terminals from Cardisoma are easily isolated following collagenase treatment and appear morphologically and electrically very similar to non-dissociated nerve endings. We have observed two types of single-channel currents not previously described. The first ('f') channel is activated by intracellular Na+ and the second ('s') by intracellular Ca2+. Both show little selectivity between Na+ and K+. In symmetrical K+, these cation channels have mean conductances of 69 and 213 pS, respectively. Furthermore, at least three types of Ca2+ channels can be reconstituted from nerve terminal membranes prepared from sinus glands. Nerve terminals can also be isolated from the rat neural lobe. These neurosecretosomes release oxytocin and vasopressin, in response to membrane depolarization, only in the presence of external Ca2+. The depolarization of the nerve endings is associated with an increase in intracellular free Ca2+ concentration and this increase, measured using a fluorescent indicator, is abolished by Ca2+ channel blockers. Channels similar in their properties to the f and s channels also exist in rat neural lobe endings. Since these channels have not been found in other neurones or neuronal structures they may be unique to peptidergic nerve terminals.
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PMID:Ionic channels and hormone release from peptidergic nerve terminals. 242 9

The effects of oxytocin and cAMP on ion transport were investigated in toad urinary bladders incubated with Ca2+-free solutions on the apical side. Under these conditions both oxytocin and cAMP markedly stimulated the movements of Na+, K+, Rb+, Cs+, Li+, and NH4+ through a pathway that is insensitive to amiloride. The amiloride-insensitive currents were inhibited by the addition of Ca2+, Sr2+, or Mg2+ to the apical solution. The movement of the monovalent cations was associated with a spontaneous Lorentzian component in the power spectrum of the fluctuation in short-circuit current. The plateau of the Lorentzian component was enhanced by oxytocin and cAMP and was depressed by divalent cations. Methohexital inhibited the stimulation of monovalent cation movements caused by oxytocin. These findings suggest that oxytocin and cAMP activate at least two kinds of ionic channels in the apical membrane of toad urinary bladder: the well-known amiloride-sensitive channel and an amiloride-insensitive channel that allows the movement of several monovalent cations and is blocked by Ca2+ and other divalent cations.
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PMID:Oxytocin and cAMP stimulate monovalent cation movements through a Ca2+-sensitive, amiloride-insensitive channel in the apical membrane of toad urinary bladder. 243 8

Previously (Van Driessche et al. 1987) we showed that small inward (mucosa towards serosa) oriented short-circuit currents (Isc) were recorded through the toad urinary bladder when the mucosal side was exposed to Ca2+ free solutions containing K+, Na+ (+ amiloride), Cs+ or Rb+ as main cation. This current component is inhibitable by micromolar concentrations of mucosal La3+ and divalent cations (Ca2+, Cd2+) and is considerably elevated by oxytocin (0.1 U/ml). The present study demonstrates that the addition of 50 nmol/l Ag+ to the mucosal medium during oxytocin treatment caused an additional large increase of the La3+-sensitive Isc component. The power density spectrum of the fluctuation in current contained a Lorentzian component which was enhanced by oxytocin treatment. The Lorentzian component disappeared as a consequence of the administration of mucosal Ag+. In experiments with Ca2+, Ba2+ or Mg2+ as principal mucosal cation, the La3+-sensitive Isc component was negligible under control conditions and during oxytocin treatment. Mucosal Ag+ (40 nmol/l) elicited a large inward oriented current which was blockable by the calcium channel blockers, La3+ and Cd2+. Also the organic calcium entry blockers, nicardipine and verapamil (10 mumol/l) depressed the inward current considerably. Noise analysis of the currents carried by divalent cations showed a La3+-sensitive noise component. Oxytocin-Ag+ activated currents could not be recorded in the absence of the divalent cations or small inorganic cations, e.g. with solutions which contained N-methyl D-glucamine (NMDG) as main mucosal cation.
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PMID:Ca2+ channels in the apical membrane of the toad urinary bladder. 244 54

1. Isolated neurosecretory nerve endings were prepared from rat neurohypophyses. The amount of vasopressin (AVP) and oxytocin released was measured by radioimmunoassay. 2. The amount of hormone release under resting conditions was not affected by external calcium (Ca2+o). Secretion decreased by ca. 50% when external sodium (Na+o) was replaced by choline or sucrose. 3. Ouabain did not modify the basal AVP release. 4. The Na+ ionophore monensin increased the release of AVP only in the presence of Na+o. This increase was maintained during prolonged exposure to the ionophore and occurred in the presence of Ca2+o only. 5. In the presence of Ca2+o, the amount of evoked hormone release was dependent on the external K+ concentration. Half-maximal activation was achieved with ca. 40 mM-K+. The K+-induced secretion was potentiated in Na+-free solution. 6. Prolonged 100 mM-K+-induced depolarization in the presence of Ca2+o gave rise to a large increase in hormone secretion which decreased with time (t1/2 = 2.5 min). The release could be reactivated after permeabilization of the nerve terminals in the presence of micromolar concentrations of Ca2+. 7. A stepwise paradigm in which Ko+ is incrementally increased to 25, 50, 75 and then 100 mM released more AVP than a prolonged exposure to 100 mM-K+. 8. Veratridine increased the amount of AVP released. This effect was considerably reduced in the absence of Nao+ and abolished in the presence of D600. 9. The depolarization-induced AVP release was blocked by different Ca2+-antagonists. Their effectiveness was nitrendipine = nicardipine greater than Cd2+ greater than Gd3+ greater than Co2+ = Mn2+. 10. The dihydropyridine Bay K 8644 potentiated both the basal and the K+-evoked AVP release. Its maximal effect was obtained with 25-50 mM-Ko+. 11. In conclusion, the isolated neurohypophysial terminals which have both Na+ and Ca2+ channels and release AVP and oxytocin upon depolarization might be an excellent system to study further the mechanisms leading to secretion of neurohormones.
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PMID:Hormone release from isolated nerve endings of the rat neurohypophysis. 245 Sep 99

1. Isolated nerve endings from rat neurohypophyses were permeabilized with digitonin in order to gain access to the cytoplasm. Release of vasopressin (AVP), oxytocin and the neurophysins was studied under different experimental conditions. 2. Hormone release, which occurred by exocytosis, was Ca2+ dependent. Half-maximal release was observed at ca. 1.7 microM-Ca2+ in contrast to ca. 300 microM for K+-induced hormone secretion from non-permeabilized neurosecretosomes. 3. Release also occurred when the neurosecretosomes were challenged with Ca2+ 20 min after digitonin treatment. This suggests that the isolated nerve endings remain permeable after treatment with digitonin. 4. Although hormone release was potentiated in the presence of ATP, and to a lesser extent with guanosine triphosphate (GTP), secretion occurred in the absence of nucleotides. 5. Replacement of K+ as the major cation by Na+ did not modify the secretory response to a Ca2+ challenge. Release, although reduced, still occurred when KCl was replaced by sucrose. 6. Compared to glutamate, Cl-, Br- and I- did not modify the Ca2+-independent release. This release was increased in the presence of SCN-. The order of effectiveness of the anions studied in inhibiting the Ca2+-dependent release was glutamate less than Br- = Cl- = I- less than SCN-. 7. Increasing the osmolarity of the perfusate inhibited the Ca2+-dependent release of AVP and oxytocin. 8. Vincristine, which binds to microtubules, had no effect on the secretory process. 9. Ca2+ dependent AVP release was partially inhibited by the calmodulin antagonist trifluoroperazine. 10. Hormone release was potentiated by the protein kinase C activator, 4-beta-phorbol 12-myristate acetate (TPA). 11. Whereas 0.2 microM-Ca2+ induced a barely significant increase in AVP release, inositol 1,4,5-triphosphate, in the continued presence of 0.2 microM-Ca2+, produced a large secretory response. 12. 4-acetamido-4'-isothiocyanostilbene-2,2'-disulphonic acid (SITS), an inhibitor of Cl- permeability, reduced the Ca2+-dependent AVP release. 13. Carbonyl cyanide m-chlorophenylhydrazone (CCCP), which reduces the transmembrane potential of isolated neurohypophysial granules, inhibited the Ca2+-dependent hormone secretion. 14. Maximal hormone release occurred at pH 6.6. 15. It is concluded that the permeabilized neurosecretosomes represent an excellent model for studying the minimal requirements for neurosecretion.
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PMID:Requirements for hormone release from permeabilized nerve endings isolated from the rat neurohypophysis. 245 Oct

1. The properties of cation movements through a previously described Ca2+-sensitive oxytocin-stimulated pathway in the apical membrane of the toad urinary bladder were further investigated. 2. In the absence of Ca2+ and other polyvalent cations in the mucosal medium, oxytocin markedly stimulated the flow of current from mucosa to serosa when the major cation in the mucosal solution was any of the following ions: Na+, K+, Rb+, Cs+ or Li+. Analysis of the current noise showed a Lorentzian component associated with the movement of these cations. 3. Ca2+ and other divalent cations in the mucosal solution depressed both the current and the Lorentzian component of the fluctuation spectra. The Michaelis-Menten constants were 2.5, 10 and 58 mumol/l for Ca2+, Sr2+ and Mg2+ respectively. 4. The dihydropyridine Ca2+ channel blockers nitrendipine (10(-5) mol/l) and nicardipine (10(-6) mol/l) inhibited the Ca2+-sensitive current. 5. Alterations of the mucosal pH showed that the current and the plateau of the Lorentzian component increased by elevating the pH from 6 to 8. The Ca2+-sensitive current was further stimulated by increasing pH to 9. However, this manoeuvre resulted in the disappearance of the Lorentzian component in the noise spectrum. 6. Increasing either mucosal [Na+] or [K+] up to 115 mmol/l did not lead to saturation of the current passing through the Ca2+-sensitive channel. In contrast the amiloride-sensitive channel showed saturating behaviour when mucosal [Na+] was increased; half-maximum current was reached when mucosal [Na+] was about 15 mmol/l. 7. When a Na+-free mucosal solution, prepared with either choline or TEA as major cation, was rapidly replaced by a solution with Na+ (115 mmol/l), the current through the Ca2+-sensitive channel increased rapidly and then remained at a nearly constant level. This behaviour is in contrast with the response of the current through the amiloride-sensitive pathway. After suddenly increasing mucosal Na+ concentration ([Na+]m), the current through this channel first increased rapidly and then declined to values of nearly 50% of the peak about 10 min after the increase in [Na+]m.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Activation and blockage of a calcium-sensitive cation-selective pathway in the apical membrane of toad urinary bladder. 245 2

1. Na+ as well as Li+ move across the apical membrane through amiloride-sensitive ionic channels. 2. K+ movements across the apical membrane occur through Ba2+- and Cs+-sensitive channels which do not allow the passage of Na+ or Li+. 3. A third pathway in the apical membrane is permeable for Na+, K+, Cs+, Rb+, NH+4 and Ti+. The currents carried by these monovalent cations are blocked by Ca2+ and divalent cations as well as La3+. 4. In the urinary bladder, the Ca2+-sensitive currents are stimulated by oxytocin, activators of cytosolic cAMP and cAMP analogues. Also the oxytocin activated currents are blocked by divalent cations and La3+. 5. Nanomolar concentrations of mucosal Ag+ activate the third channel and open the pathway for movements of Ca2+, Ba2+ and Mg2+, which are known to permeate through Ca2+ channels in excitable tissues.
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PMID:Cation-selective channels in amphibian epithelia: electrophysiological properties and activation. 246 Feb 85

Outward rectifying, cation channels were observed in the epithelial cells of the urinary bladder of the toad. Bufo marinus. As studied in isolated cells using the patch-clamp technique, the channel has an average conductance of 24 and 157 pS for pipette potentials between 0 and +60 mV and -60 to -100 mV, respectively, when the major cation in both bath and pipette solutions is K+. The conductance of the channel decreases with increasing dehydration energy of the permeant monovalent cation in the order Rb+ = K+ greater than Na+ greater than Li+. Reversal potentials near zero under biionic conditions imply that the permeabilities for all four of these cations are similar. The channel is sensitive to quinidine sulfate but not to amiloride. It shares several pharmacological and biophysical properties with an outwardly-rectifying, vasopressin-sensitive apical K+ conductive pathway described previously for the toad urinary bladder. We demonstrate, in both single-channel and whole-bladder studies, that the outward rectification is a consequence of interaction of the channel with extracellular divalent cations, particularly Ca2+, which blocks inward but not outward current. Various divalent cations impart different degrees of outward rectification to the conductive pathway. Concentrations of Mg2+ and Ca2+ required for half-maximal effect are 3 X 10(-4) and 10(-4) M, respectively. For Co2+ the values are 10(-6) M at +50 mV and a 10(-4) M at +200 mV. The mechanism of blockade by divalent cations is not established, but does not seem to involve a voltage-dependent interaction in which the blocker penetrates the transmembrane electric field. In the absence of divalent cations in the mucosal solution, the magnitudes of inward current carried by Rb+, K+, Na+ and Li+ through the apical K+ pathway at any transepithelial voltage, are in the same order as in the single-channel studies. We propose that the cation channel observed by us in isolated epithelial cells is the single-channel correlate of the vasopressin-sensitive apical K+ conductive pathway in the toad urinary bladder and is also related to the oxytocin- and divalent cation-sensitive apical conductivity observed in frog skin and urinary bladder.
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PMID:Extracellular Ca2+ controls outward rectification by apical cation channels in toad urinary bladder: patch-clamp and whole-bladder studies. 246 99

We investigated the effect of forskolin on Cl- movements across the isolated epithelium of frog skin. With Cl- on both sides, forskolin (50 mumol/l) increased the transepithelial conductance considerably and elicited significant Cl- secretion. Establishing transepithelial Cl- gradients markedly increased the Cl- currents (ICl). During forskolin treatment, the power density spectra (PDS) of the fluctuation in transepithelial current contained a Lorentzian component that depended on the presence of Cl- in the bathing solutions. Mucosal as well as serosal diphenylamine-2-carboxylic acid (DPC; 1 mmol/l) partially depressed ICl as well as the Lorentzian noise component. Microelectrode recordings from cells involved in transepithelial Na+ absorption showed that forskolin activates gated Cl- channels in a cellular pathway in parallel with the Na+-transporting granulosum cells of the frog skin. The activation of the Cl- -dependent currents and Lorentzian noise was rather variable, and adaptation of the animals to solutions that contained 40 or 60 mmol/l NaCl increased the sensitivity to forskolin. In skins of salt-adapted animals, oxytocin (0.1 U/ml) also slightly activated the Cl- pathway. On the other hand, oxytocin and 8-(4-chlorophenylthio)adenosine 3',5'-cyclic monophosphate (CPT-cAMP; 1 mmol/l) were without effect in control skins.
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PMID:Forskolin activates gated Cl- channels in frog skin. 247 70

Intracellular free calcium concentrations were measured directly in rat myometrial cells loaded with fura-2. The basal concentrations of calcium were 148 +/- 5.0 and 137 +/- 3.7 nM in the presence and absence of 1 mM extracellular calcium, respectively. Oxytocin, carbachol, and norepinephrine rapidly and transiently increased intracellular free calcium, with half-maximal effects at 0.19, 9.9, and 5.3 microM, respectively. The maximal effects of these agents were reduced by 57%, 32%, and 36%, respectively, when the extracellular calcium was replaced by 2 mM EGTA. Pretreatment with pertussis toxin partially (47-57%) inhibited the contractant-induced increase in intracellular free calcium in the presence of 1 mM extracellular CaCl2 and produced an even greater inhibition (76-98%) in the absence of extracellular calcium. Pretreatment with D600 (30 microM) or amiloride (50 microM) and reduction of extracellular sodium did not affect the oxytocin-induced calcium increase. However, adenosine and the A2-receptor agonist N-ethylcarboxamidoadenosine did attenuate the effect of oxytocin in a dose-dependent manner. These data represent the first direct evidence that oxytocin, carbachol, and norepinephrine increase the intracellular free calcium concentration in the rat myometrium. The data suggest that contractants mobilize calcium from both extracellular and intracellular sources, the latter involving a pertussis toxin-sensitive mechanism.
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PMID:Changes in intracellular free calcium in isolated myometrial cells: role of extracellular and intracellular calcium and possible involvement of guanine nucleotide-sensitive proteins. 249 4


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