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Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Calcium currents in rabbit area postrema neurons were studied with the perforated patch-clamp technique. Experimental conditions eliminated Na+ and K+ currents and identified both low- and high-threshold voltage-activated calcium currents. 2. Low-threshold, T-type calcium currents were observed in 64% of the area postrema neurons recorded. This current activated near -60 mV and had an average peak amplitude of -36.2 +/- 5 pA (mean +/- SE) at -40 mV. This current began rapid inactivation near -95 mV, reached half-maximal inactivation at -71 mV and was totally inactivated by -40 mV. 3. A high-threshold transient current was recorded in all area postrema neurons, which consisted of both a transient and sustained component. This current was present at voltages greater than -40 mV and the transient component of this current was responsible for the majority of the total Ca2+ current. 4. Nickel ions (10 microM) effectively reduced both the T-type current and the high-threshold current. Cadmium ions (100 microM) effectively reduced the high-threshold current while having insignificant effects on the low-threshold current. 5. Application of the dihydropyridine antagonist nimodipine (1-10 microM) had no effect on either the low- or high-threshold voltage-activated calcium Ca2+ in area postrema neurons. In addition, application of omega-conotoxin-GVIA (2-10 microM) was also without effect on either the low- or high-threshold voltage-activated Ca2+ current, suggesting that area postrema neurons possess neither L- or N-type voltage-activated Ca2+ currents. 6. Application of omega-conotoxin MVIIC (10 microM) significantly inhibited the peak high-threshold Ca2+ current by 65.4% suggesting that area postrema neurons do possess a omega-conotoxin MVIIC-sensitive high-threshold Ca2+ channel. 7. Arg-vasopressin (150 nM) significantly increased the transient component of the high-threshold Ca2+ current but had little effect on either the low-threshold or the high-threshold sustained component.
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PMID:Area postrema voltage-activated calcium currents. 882 47

The effects of extracellular Mg2+ on receptor-mediated Ca(2+)-permeable non-selective cation currents were investigated in a cultured aortic smooth muscle cell line (A7r5) from rat thoracic aorta, using the whole-cell voltage-clamp technique. Under the Cs(+)-containing internal solution, both vasopressin and endothelin-1 (100 nM) activated a long-lasting inward current with a high noise level. The reversal potential of these agonists-induced current was approximately +0 mV, and was not significantly altered by the replacement of [Cl-]i or [Cl-]o, suggesting that the inward current was a cation-selective channel. La3+ and Cd2+ (1 mM) almost completely abolished the vasopressin or endothelin-induced non-selective cation current; however, nifedipine (10 microM) failed to inhibit it significantly. Extracellular Mg2+ (3-20 mM) also markedly inhibited the vasopressin- or endothelin-induced non-selective cation current in a concentration-dependent manner. When a non-hydrolysable GTP-analogue, GTP gamma S (1 mM), was applied from the patch pipette, the non-selective cation current was gradually activated even in the absence of agonist (vasopressin or endothelin-1), probably due to the direct activation of GTP-binding proteins coupled to the receptors. Extracellular Mg2+ (3-20 mM) also suppressed the activation of non-selective cation current induced by GTP gamma S, suggesting that the inhibitory sites of Mg2+ are not located on the receptors. These results suggest that extracellular Mg2+ inhibits receptor-mediated non-selective cation current, which may contribute to the relaxation effects of Mg2+ in vascular smooth muscle cells.
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PMID:Extracellular Mg2+ inhibits receptor-mediated Ca(2+)-permeable non-selective cation currents in aortic smooth muscle cells. 904 6

1. The effects of omega-3 polyunsaturated fatty acids on receptor-mediated non-selective cation current (Icat) and K+ current were investigated in aortic smooth muscle cells from foetal rat aorta (A7r5 cells). The whole-cell voltage clamp technique was employed. 2. With a K(+)-containing solution, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA, 30 microM) produced an outward current at a holding potential of -40 mV. This response was inhibited by tetraethylammonium (20 mM) or Cs+ in the patch pipette solution, and the reversal potential of the EPA-induced current followed the K+ equilibrium potential in a near Nernstian manner. 3. Under conditions with a Cs(+)-containing pipette solution, both vasopressin and endothelin-1 (100 nM) induced a long-lasting inward current at a holding potential of -60 mV. The reversal potential of these agonist-induced currents was about +0 mV, and was not significantly altered by the replacement of the extracellular or intracellular Cl+ concentration, suggesting that the induced current was a cation-selective current (Icat). 4. La3+ and Cd2+ (1 mM) completely abolished these agonist-induced Icat, but nifedipine (10 microM) failed to inhibit it significantly. 5. omega-3 polyunsaturated fatty acids (3-100 microM), EPA, DHA and docosapentaenoic acids (DPA), inhibited the agonist-induced Icat in a concentration-dependent manner. The potency of the inhibitory effect was EPA > DHA > DPA, and the half maximal inhibitory concentration (IC50) of EPA was about 7 microM. 6. Arachidonic and linoleic acids (10, 30 microM) showed a smaller inhibitory effect compared to omega-3 fatty acids. Also, oleic and stearic acids (30 microM) did not show a significant inhibitory effect on Icat. 7. A similar inhibitory action of EPA was observed when Icat was activated by intracellularly applied GTP gamma S in the absence of agonists, suggesting that the site of action of omega-3 fatty acids is not located on the receptor. 8. These results demonstrate that omega-3 polyunsaturated fatty acids can activate a K+ current and also effectively inhibit receptor-mediated non-selective cation currents in rat A7r5 vascular smooth muscle cells. Thus, the data suggest that omega-3 fatty acids may play an important role in the regulation of vascular tone.
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PMID:Inhibitory effects of omega-3 polyunsaturated fatty acids on receptor-mediated non-selective cation currents in rat A7r5 vascular smooth muscle cells. 910 14

1. Intracellular recordings were obtained in vitro from oxytocin and vasopressin neurones from dioestrous and lactating female rats. Oxytocin neurones were characterized under current clamp by the expression of a depolarization-activated, sustained outward rectification (SOR) and a rebound depolarization (RD). 2. An increment in extracellular K+ shifted the expression of the SOR and RD towards a more depolarized membrane potential, indicating that the mechanisms underlying these events are dependent on extracellular potassium. 3. The SOR and RD were blocked by external tetraethylammonium (10 mM) and Ba2+ (0.1-0.5 mM). Cs+ (2 mM) blocked the hyperpolarization-activated inward rectification without affecting the expression of the SOR and RD. 4. The SOR was not affected by 4-aminopyridine (6 mM). However, the rebound amplitude was significantly enhanced, indicating that the activation of a transient outward current interacts with the expression of the rebound. 5. Iberiotoxin (100 nM) and apamin (50 nM), toxins known to block some calcium-dependent potassium conductances, did not affect the expression of the SOR and RD. 6. The SOR and RD were significantly reduced by Cd2+ (0.5 mM) but not by Ni2+ (0.25 mM). 7. Muscarine (10 microM) did not affect the SOR or the RD. 8. These results indicate that the SOR and RD depend upon a depolarization-activated, sustained outward potassium current, which might be calcium dependent. A current with these characteristics has never been described before in the magnocellular system. Voltage-clamp experiments are needed to completely characterize this potassium conductance selectively expressed by oxytocin neurones.
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PMID:Sustained outward rectification of oxytocinergic neurones in the rat supraoptic nucleus: ionic dependence and pharmacology. 914 33

The actions of vasopressin on acutely dissociated neurons within the rat horizontal limb of the diagonal band of Broca were examined using the whole-cell patch-clamp technique. Vasopressin elicited two distinct responses in 45 of 62 neurons. In one group of cells, 300 nM vasopressin decreased voltage-activated outward currents (26/45 cells) whereas in a second group, vasopressin increased outward currents (19/45 cells). The vasopressin-mediated decrease in outward currents was blocked by 1 microM Manning compound, a V1 receptor antagonist, suggesting that this response was mediated via V1 receptors. In contrast, the vasopressin-induced increase in outward current was blocked by 1 microM d(CH2)5)1,D-Ile2,Ile4,Arg8,Ala9, a V2 receptor antagonist, indicating that V2 receptor activation underlies this second response. When cells were perfused with 0 Ca2+/50 microM Cd2+, application of vasopressin did not cause any change in voltage-activated outward currents, suggesting that vasopressin modulates a calcium-dependent conductance. In the presence of 25 nM charybdotoxin, an Ic channel antagonist, vasopressin application did not influence outward currents, indicating that vasopressin modulates Ic. Currents through voltage-gated calcium channels which are responsible for activation of Ic were unaffected by vasopressin, suggesting a direct effect of vasopressin on Ic channels. These observations indicate a differential modulation of Ic channels by vasopressin via V1 and V2 receptors in the horizontal limb of the diagonal band of Broca. Our data also demonstrate the ionic mechanisms whereby vasopressin may act at V1 for V2 receptors to influence the excitability of the horizontal limb of the diagonal band of Broca neurons.
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PMID:Vasopressin receptor subtypes differentially modulate calcium-activated potassium currents in the horizontal limb of the diagonal band of Broca. 930 Apr 1

1. The role of voltage-dependent Ca2+ channels during vasopressin and oxytocin actions on their respective neurones has been analysed by measuring intracellular Ca2+ concentration ([Ca2+]i) in individual, freshly dissociated magnocellular neurones from rat supraoptic nucleus (SO) using microspectrofluorimetry. 2. Pre-incubation of vasopressin-sensitive neurones with Cd2+ (100 microM), a non-discriminatory high-voltage-activated Ca2+ channel antagonist, or Ni2+ (50 microM), a blocker of T-type Ca2+ current, reduced [Ca2+]i responses by 77 and 19%, respectively. When Cd2+ was given together with Ni2+, the response was blocked by 92%. Similarly, when Ni2+ was pre-incubated with Cd2+, the response was blocked by approximately 84%. 3. Exposure of vasopressin sensitive neurones to a specific Ca2+ channel blocker, nicardipine (L-type) reduced vasopressin responses by 48% at 1 microM and 62% at 5 microM. Similarly, omega-conotoxin GVIA (omega-CgTX, N-type; 500 nM) inhibited the response by 46% with a stronger inhibition (75%) at 800 nM. By contrast, neither omega-agatoxin IVA (omega-Aga IVA; 300 nM), which blocks both P- and Q-type channels, nor synthetic omega-conotoxin MVIIC (omega-MVIIC; 100 or 500 nM), a Q-type blocker, affected vasopressin-induced [Ca2+]i responses. These antagonists, given together (nicardipine 5 microM + omega-CgTX 800 nM + omega-Aga IVA 300 nM), decreased vasopressin-induced [Ca2+]i responses by 76%. 4. In vasopressin-sensitive neurones, the presence of both nicardipine and omega-CgTX, reduced the K(+)-evoked [Ca2+]i increase by 61%. This blockade was increased by a further 21% with omega-Aga IVA, suggesting that N-, L- and P-type channels contribute to the depolarization-induced [Ca2+]i rise. In addition, omega-MVIIC alone reduced the K(+)-evoked [Ca2+]i release by 24%. Also the remaining K+ responses were further reduced by 60% when pre-incubated with L-N- and P-type blockers, suggesting the involvement of Q-type channels. 5. In oxytocin-sensitive neurones, the peak amplitude of the [Ca2+]i response was not affected by Cd2+ alone, by combined Cd2+ and Ni2+, or by the mixture of nicardipine, omega-CgTX and omega-Aga IVA. By contrast, the responses evoked by depolarization with K+ were blocked by Cd2+. Both nicardipine and omega-CgTX blocked 65% of K+ response and an additional block of approximately 18% was obtained with omega-Aga IVA, suggesting the involvement of L-, N- and P-type channels. In combination, these antagonists strongly inhibited (approximately 80% reduction) the K+ responses. Further reduction to 18% was made by the Q-type blocker omega-MVIIC. Pre-incubation with L-, N- and P-type blockers caused an additional block of 71%. 6. Some supraoptic neurones (5-10%) responded to both vasopressin and oxytocin, with only the [Ca2+]i responses induced by vasopressin blocked (> 90% inhibition) by the mixture of Ca2+ channel antagonists. 7. In conclusion, both vasopressin and oxytocin magnocellular SO neurones have been shown to express T-, L-, N-, P-, Q- and R-type Ca2+ channels in their somata. Our results show that the vasopressin-induced [Ca2+]i increase in vasopressin-sensitive neurones is mediated by L-, N- and T-type Ca2+ channels and not by P- and Q-type channels; Ca2+ channels are not involved in oxytocin action on oxytocin-sensitive neurones and L-, N-, P- and Q-type channels control the K(+)-induced [Ca2+]i increase in SO neurones.
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PMID:L-, N- and T- but neither P- nor Q-type Ca2+ channels control vasopressin-induced Ca2+ influx in magnocellular vasopressin neurones isolated from the rat supraoptic nucleus. 930 70

The molluscan vasopressin/oxytocin analogue Lys-conopressin excites neurons in the anterior lobe of the right cerebral ganglion of the snail Lymnaea stagnalis. Persistent inward currents that underlie the excitatory response were studied with the use of voltage-ramp protocols in the identified neuron RCB1 and other anterior lobe neurons. Under whole cell voltage-clamp conditions, two types of conopressin-activated current could be distinguished on the basis of their voltage dependence: 1) a pacemaker-like current that was activated at potentials above -40 mV (high-voltage-activated current, I(HVA)) and 2) an inward current that was activated at all potentials between -90 and +10 mV (low-voltage-activated current, I(LVA)). Ion substitution experiments indicate that sodium is the main charge carrier for I(HVA) and I(LVA). Both currents are differentially affected by cadmium. I(HVA) and I(LVA) differ in dose dependence, with median effective concentration values of 7.7 x 10(-8) M and 2.2 x 10(-7) M, respectively. Vasopressin and oxytocin act as weak agonists for the conopressin responses. The kinetics of desensitization and washout of I(HVA) and I(LVA) are different. The HVA response shows little desensitization, whereas the LVA response desensitizes within minutes (time constant 80 +/- 28 s, mean +/- SD). The time constant of washout on removal of conopressin is 159 +/- 63 s for I(HVA) and 36 +/- 13 s for I(LVA). These results suggest that two distinct conopressin receptors are involved in the activation of both currents. The conopressin-activated currents induce or enhance a region of negative slope resistance in the steady-state current-voltage relation. They differ from a third persistent inward current that is carried by calcium and completely blocked by cadmium. The presumed functional roles of these currents, possibly including autoregulation, are discussed.
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PMID:Vasopressin/oxytocin-related conopressin induces two separate pacemaker currents in an identified central neuron of Lymnaea stagnalis. 931 Apr 29

1. The effect of externally applied ATP on cytosolic free Ca2+ concentration ([Ca2+]i) was tested in single isolated rat neurohypophysial nerve terminals by fura-2 imaging. The release of vasopressin (AVP) and oxytocin (OT) upon ATP stimulation was also studied from a population of terminals using specific radioimmunoassays. 2. ATP evoked a sustained [Ca2+]i increase, which was dose dependent in the 1-100 microM range (EC50 = 4.8 microM). This effect was observed in only approximately 40 % of the terminals. 3. Interestingly, ATP, in the same range (EC50 = 8.6 microM), evoked AVP, but no significant OT, release from these terminals. 4. Both the [Ca2+]i increase and AVP release induced by ATP were highly and reversibly inhibited by suramin, suggesting the involvement of a P2 purinergic receptor in the ATP-induced responses. Pyridoxal-5-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), another P2 purinergic receptor antagonist, strongly reduced the ATP-induced [Ca2+]i response. 5. To further characterize the receptor, different agonists were tested, with the following efficacy: ATP = 2-methylthio-ATP > ATP-gamma-S > alpha, beta-methylene-ATP > ADP. The compounds adenosine, AMP, beta, gamma-methylene-ATP and UTP were ineffective. 6. The ATP-dependent [Ca2+]i increase was dependent on extracellular Ca2+ concentration ([Ca2+]o). Fluorescence-quenching experiments with Mn2+ showed that externally applied ATP triggered a Mn2+ influx. The ATP-induced [Ca2+]i increase and AVP release were independent of and additive to a K+-induced response, in addition to being insensitive to Cd2+. The ATP-induced [Ca2+]i increase was strongly reduced in the presence of Gd3+. These results suggest that the observed [Ca2+]i increases were elicited by Ca2+ entry through a P2X channel receptor rather than via a voltage-dependent Ca2+ channel. 7. We propose that ATP, co-released with neuropeptides, could act as a paracrine-autocrine messenger, stimulating, via Ca2+ entry through a P2X2 receptor, the secretion of AVP, in particular, from neurohypophysial nerve terminals.
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PMID:ATP-evoked increases in [Ca2+]i and peptide release from rat isolated neurohypophysial terminals via a P2X2 purinoceptor. 967 66

The contribution of Ca(2+)-activated K(+) channels to hyperpolarizing after-potentials (HAP) of action potentials, to spike-frequency adaptation and thus to the shaping of discharge pattern, was examined in rat supraoptic magnocellular neurosecretory cells. In addition, the expression of BK channels and SK3 subunits of SK channels was studied using double immunofluorescence detection. The presence of BK channels and SK3 subunits was detected in many supraoptic neurones containing either vasopressin or oxytocin. Current-clamp recordings of current-induced spike trains revealed that HAPs comprise a fast and a slow HAP (fHAP and sHAP). Correlation analyses revealed that the increase of the fHAP in amplitude and spike broadening were correlated to a moderate gradual increase of the interspike interval and thus to weak spike-frequency adaptation. By contrast, marked prolongation of the interspike interval and strong spike-frequency adaptation depended on the appearance and on the amplitude of the sHAP. The sHAP and spike-frequency adaptation were blocked by cadmium, as well as by the SK channel antagonist apamin. The fHAP was attenuated by the BK channel antagonist iberiotoxin (IbTX), by the BK/IK channel antagonist charybdotoxin (ChTX) and by apamin. ChTX attenuated fHAPs throughout the entire spike train. By contrast, the IbTX-induced attenuation of the fHAP was restricted to the initial part of the spike train, while the apamin-induced attenuation slowly increased with the progression of the spike train. These results suggest that strong spike-frequency adaptation in supraoptic neurones essentially depends on the generation of the sHAP by activation of SK channels. Comparison of effects of IbTX, ChTX and apamin suggests a complementary contribution of SK-, BK- and IK-channels to fHAPs.
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PMID:Contribution of Ca2+-activated K+ channels to hyperpolarizing after-potentials and discharge pattern in rat supraoptic neurones. 1521 61

ATP increases intracellular calcium concentration ([Ca(2+)](i)) in supraoptic nucleus (SON) neurons in hypothalamo-neurohypophyseal system explants loaded with the Ca(2+)-sensitive dye, fura 2-AM. Involvement of P2X purinergic receptors (P2XR) in this response was anticipated, because ATP stimulation of vasopressin release from hypothalamo-neurohypophyseal system explants required activation of P2XRs, and activation of P2XRs induced an increase in [Ca(2+)](i) in dissociated SON neurons. However, the ATP-induced increase in [Ca(2+)](i) persisted after removal of Ca(2+) from the perifusate ([Ca(2+)](o)). This suggested involvement of P2Y purinergic receptors (P2YR), because P2YRs induce Ca(2+) release from intracellular stores, whereas P2XRs are Ca(2+)-permeable ion channels. Depletion of [Ca(2+)](i) stores with thapsigargin (TG) prevented the ATP-induced increase in [Ca(2+)](i) in zero, but not in 2 mM [Ca(2+)](o), indicating that both Ca(2+) influx and release of intracellular Ca(2+) contribute to the ATP response. Ca(2+) influx was partially blocked by cadmium, indicating a contribution of voltage-gated Ca(2+) channels. PPADS (pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid), and iso-PPADS, P2XR antagonists, attenuated, but did not abolish, the ATP-induced increase in [Ca(2+)](i). Combined treatment with PPADS or iso-PPADS and TG prevented the response. A cocktail of P2YR agonists consisting of UTP, UDP, and 2-methylthio-ADP increased [Ca(2+)](i) (with or without tetrodotoxin) that was markedly attenuated by TG. 2-Methylthio-ADP alone induced consistent and larger increases in [Ca(2+)](i) than UTP or UDP. MRS2179, a specific P2Y(1)R antagonist, eliminated the response to ATP in zero [Ca(2+)](o). Thus, both P2XR and P2YR participate in the ATP-induced increase in [Ca(2+)](i), and the P2Y(1)R subtype is more prominent than P2Y(2)R, P2Y(4)R, or P2Y(6)R in SON.
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PMID:ATP increases intracellular calcium in supraoptic neurons by activation of both P2X and P2Y purinergic receptors. 1697 29


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