Involvement of a GTP-binding protein in mediation of serotonin and acetylcholine responses in Xenopus oocytes injected with rat brain messenger RNA

Dascal, Nathan; Ifune, Catherine; Hopkins, Rosemary S.; Snutch, Terry P.; Lübbert, Hermann; Davidson, Norman; Lester, Henry A.

doi:10.1016/0169-328x(86)90026-4

Cited by 113 publications

(56 citation statements)

References 33 publications

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“…1 Aii). Similar biphasic time courses for the activation of the calcium-dependent inward chloride current have been described for the activation of a range of G-proteincoupled receptors expressed in Xenopus oocytes (Dascal et al, 1986;Yakel et al, 1993). Uninjected control oocytes showed no inward currents in response to dopamine application (data not shown).…”

Section: Time Course Of Responsesmentioning

confidence: 67%

Agonist-Specific Coupling of a ClonedDrosophila melanogasterD1-Like Dopamine Receptor to Multiple Second Messenger Pathways by Synthetic Agonists

et al. 1997

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The mechanism of coupling of a cloned Drosophila D1-like dopamine receptor, DopR99B, to multiple second messenger systems when expressed in Xenopus oocytes is described. The receptor is coupled directly to the generation of a rapid, transient intracellular Ca 2ϩ signal, monitored as changes in inward current mediated by the oocyte endogenous Ca 2ϩ -activated chloride channel, by a pertussis toxin-insensitive G-proteincoupled pathway. The more prolonged receptor-mediated changes in adenylyl cyclase activity are generated by an independent G-protein-coupled pathway that is pertussis toxinsensitive but calcium-independent, and G ␤␥ -subunits appear to be involved in the transduction of this response. This is the first evidence for the direct coupling of a cloned D1-like dopamine receptor both to the activation of adenylyl cyclase and to the initiation of an intracellular Ca 2ϩ signal. The pharmacological profile of both second messenger effects is identical for a range of naturally occurring catecholamine ligands (dopamine Ͼ norepinephrine Ͼ epinephrine) and for the blockade of dopamine responses by a range of synthetic antagonists. However, the pharmacological profiles of the two second messenger responses differ for a range of synthetic agonists. Thus, the receptor exhibits agonist-specific coupling to second messenger systems for synthetic agonists. This feature could provide a useful tool in the genetic analysis of the roles of the multiple second messenger pathways activated by this receptor, given the likely involvement of dopamine in the processes of learning and memory in the insect nervous system.

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Section: Time Course Of Responsesmentioning

confidence: 67%

Agonist-Specific Coupling of a ClonedDrosophila melanogasterD1-Like Dopamine Receptor to Multiple Second Messenger Pathways by Synthetic Agonists

et al. 1997

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“…Blood sera from vertebrate species are reported to elicit oscillatory Cl-currents in Xenopus oocytes (Tigyi, Dyer, Matute & Miledi, 1990). In the present study, 0 3 mg/ml bovine blood albumin (Fraction V; Wako Pure Chemical Industries, Japan) was used as a stabilizer (see Dascal et al 1986;Cohen-Armon et al 1989) for testing the effect of pertussis toxin (PTX). The possibility that the inhibition of the ACh response was not due to the blockade of G proteins by PTX but by depletion of the intracellular Ca2" stores by albumin can be excluded because (a) the albumin used in the present study did not elicit any currents on its own (n = 5), (b) ionomycin induced inward-current responses in Xenopus oocytes which were treated with albumin and PTX (Fig.…”

Section: Discussionmentioning

confidence: 99%

Mechanism of release of Ca2+ from intracellular stores in response to ionomycin in oocytes of the frog Xenopus laevis.

Yoshida

Plant

1992

The Journal of Physiology

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SUMMARY1. The mechanism of Ca2+ release from intracellular stores was studied in defolliculated Xenopus laevis oocytes by measuring whole-cell currents using the twoelectrode voltage-clamp method.2. The extracellular application of ionomycin, a selective Ca2+ ionophore, evoked an inward current consisting of a spike-like fast component followed by a long-lasting slow component with few superimposed current oscillations (fluctuations). The ionomycin response occurred in a dose-dependent manner and was dependent on Cl-.3. No apparent refractory period was observed for repetitively evoked small ionomycin responses when the concentration of ionomycin was low (0 1 ftM). In contrast, a larger ionomycin response (1 ,lM), consisting of fast and slow components, was followed by refractory period. Washing for 50-90 min was necessary for full recovery of the ionomycin response.4. The response to ionomycin was suppressed by the extracellular application of acetoxymethyl ester of bis-(O-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid (BAPTA AM, 1-10 ,tM), a membrane-permeable intracellular Ca2+ chelator.5. The ionomycin response was not affected by pertussis toxin (PTX, 0-3-2-0,tg/ml), a blocker of guanine nucleotide-binding regulatory proteins (G proteins). In contrast, the response to acetylcholine (ACh), which is known to occur via a G protein, was suppressed by PTX.6. The fast component was not affected by removing Ca2+ from the bathing medium or by replacing extracellular Ca2+ with Ba2+ or Mn2+ (all of these solutions were supplemented with 2 mm EGTA), whereas the slow component was suppressed.7 S. YOSHIDA AND S. PLANT cellularly applied ionomycin did not evoke an appreciable membrane current. In contrast, ionomycin evoked a small inward current when it was applied after an inward-current response evoked by 1P3 injection, whereas a second injection of 1P3 did not evoke any appreciable current.8. The results indicate that (a) ionomycin releases Ca2+ from its intracellular stores without the involvement of G proteins, resulting in activation of Ca2+-activated Clchannels, (b) ionomycin mainly acts on the same intracellular Ca2+ stores as 'P3, and (c) entry of Ca2+ from outside the cell considerably contributes to the slow component of the ionomycin response, whereas its fast component is predominantly dependent on the release of Ca2+ from the intracellular stores.

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“…To test the hypothesis that trkB activation increased GAP activity (rather than decreasing G␤␥ binding affinity for Kir3) we inhibited GTP hydrolysis by injecting GTP␥S, a non-hydrolyzable analogue of GTP (19). If Kir3 deactivation rate was controlled solely by G␤␥ dissociation and not G␤␥ sequestration by G␣ i ⅐GDP, then BDNF-accelerated deactivation could result from a reduction in G␤␥ affinity for the channel.…”

Section: Fig 1 Trkb Accelerates Kir3 Deactivationmentioning

confidence: 99%

N-terminal Tyrosine Residues within the Potassium Channel Kir3 Modulate GTPase Activity of Gαi

Ippolito

Temkin

Rogalski

et al. 2002

Journal of Biological Chemistry

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trkB activation results in tyrosine phosphorylation of N-terminal Kir3 residues, decreasing channel activation. To determine the mechanism of this effect, we reconstituted Kir3, trkB, and the mu opioid receptor in Xenopus oocytes. Activation of trkB by BDNF (brainderived neurotrophic factor) accelerated Kir3 deactivation following termination of mu opioid receptor signaling. Similarly, overexpression of RGS4, a GTPaseactivating protein (GAP), accelerated Kir3 deactivation. Blocking GTPase activity with GTP␥S also prevented Kir3 deactivation, and the GTP␥S effect was not reversed by BDNF treatment. These results suggest that BDNF treatment did not reduce Kir3 affinity for G␤␥ but rather acted to accelerate GTPase activity, like RGS4. Tyrosine phosphatase inhibition by peroxyvanadate pretreatment reversibly mimicked the BDNF/trkB effect, indicating that tyrosine phosphorylation of Kir3 may have caused the GTPase acceleration. Tyrosine to phenylalanine substitution in the N-terminal domain of Kir3.4 blocked the BDNF effect, supporting the hypothesis that phosphorylation of these tyrosines was responsible. Like other GAPs, Kir3.4 contains a tyrosine-arginine-glutamine motif that is thought to function by interacting with G protein catalytic domains to facilitate GTP hydrolysis. These data suggest that the N-terminal tyrosine hydroxyls in Kir3 normally mask the GAP activity and that modification by phosphorylation or phenylalanine substitution reveals the GAP domain. Thus, BDNF activation of trkB could inhibit Kir3 by facilitating channel deactivation.The family of G protein-activated potassium channels (Kir3 or GIRK) 1 is a principal effector mediating the actions of a wide range of pertussis toxin-sensitive, G protein-coupled receptors (GPCR) (1). Channel activation provides key regulation of both cardiac and neuronal excitability. The activity of this channel is controlled by a large number of modulators including phosphatidylinositol bisphosphate, Na ϩ , eicosanoids, ATP, Mg 2ϩ , and phosphorylation (1-6). For example, in a previous study (7), we found that tyrosine phosphorylation of Kir3 resulted in channel inhibition. Brain-derived neurotrophic factor (BDNF) activation of trkB receptors caused the phosphorylation of specific tyrosine residues in the N-terminal domain of Kir3.1 and Kir3.4, reducing basal channel conductance. G␤␥, released by opioid receptor activation, overcame the inhibition and evoked the original maximal effect. The results suggest that channel phosphorylation regulates the specific interaction with G␤␥, but the mechanism of this effect is unclear. However, the finding may be physiologically significant because tyrosine kinase cascades initiated by neurotrophic factors such as BDNF and nerve growth factor are up-regulated under conditions such as inflammation (8). It is possible that tyrosine phosphorylation of Kir3 may mediate neuronal excitability in conjunction with GPCRs under conditions of inflammation. The goal of the present study was to define the mechanism responsible for BDNF inhib...

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Involvement of a GTP-binding protein in mediation of serotonin and acetylcholine responses in Xenopus oocytes injected with rat brain messenger RNA

Cited by 113 publications

References 33 publications

Agonist-Specific Coupling of a ClonedDrosophila melanogasterD1-Like Dopamine Receptor to Multiple Second Messenger Pathways by Synthetic Agonists

Agonist-Specific Coupling of a ClonedDrosophila melanogasterD1-Like Dopamine Receptor to Multiple Second Messenger Pathways by Synthetic Agonists

Mechanism of release of Ca2+ from intracellular stores in response to ionomycin in oocytes of the frog Xenopus laevis.

N-terminal Tyrosine Residues within the Potassium Channel Kir3 Modulate GTPase Activity of Gαi

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