Desensitization of the response to thyrotropin-releasing hormone in Xenopus oocytes is an amplified process that precedes calcium mobilization

Lipinsky, Dafna; Nussenzveig, Daniel R.; Gershengorn, M C; Oron, Yoram

doi:10.1007/bf00374158

Cited by 12 publications

(27 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…After injection, oocytes were maintained for additional 48-72 h in NDE96 (Shapira et al, 1998). Where desired, oocytes were injected with M1-R or thyrotropin-releasing hormone receptor (TRH-R) transcripts (2-10 ng/oocyte) to produce the expression of the appropriate receptor in 48-72 h (Lipinsky et al, 1995;Shapira et al, 1998).…”

Section: Handling Of Oocytesmentioning

confidence: 99%

“…We have previously studied rapid homologous desensitization of native LPA-Rs or expressed TRH-Rs (Lipinsky et al, 1995;Itzhaki Van-Ham et al, 2004a). We also described heterologous rapid desensitization of threshold concentrations of ACh or TRH on subsequent responses to high TRH or ACh, respectively (Lipinsky et al, 1995).…”

Section: Rapid Heterologous Desensitization Of Responses In Xenopus Omentioning

confidence: 99%

“…Receptor-linked activation of PKA or PKC, via an increase of second messengers, often results in phosphorylation of additional receptors or of proteins participating in a common transduction pathway. This is a well established example of mechanism for heterologous desensitization (Connolly et al, 1986;Lipinsky et al, 1995;Haga et al, 1996;Yu and Hinkle, 1997;Cordeaux and Hill, 2002;Ally et al, 2003). Although numerous examples of heterologous desensitization are available, we were the first to demonstrate that thyrotropin-releasing hormone (TRH) induced a novel type of rapid heterologous desensitization of acetylcholine (ACh) responses in Xenopus oocytes (Lipinsky et al, 1995).…”

mentioning

confidence: 98%

“…Cross-talk between G-protein-coupled receptors (GPCRs) was described in many publications (Lipinsky et al, 1995;Chuang et al, 1996;Selbie and Hill, 1998;Marinissen and Gutkind, 2001;Cordeaux and Hill, 2002;Werry et al, 2003). Receptor-linked activation of PKA or PKC, via an increase of second messengers, often results in phosphorylation of additional receptors or of proteins participating in a common transduction pathway.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Go G‐proteins mediate rapid heterologous desensitization of G‐protein coupled receptors in Xenopus oocytes

Van-Ham

Oron

2005

Journal Cellular Physiology

Self Cite

View full text Add to dashboard Cite

We have shown previously that responses to lysophosphatidic acid (LPA) in Xenopus oocytes exhibit pronounced rapid homologous desensitization mediated by Go family of G-proteins (Itzhaki-Van Ham et al., 2004, J Cell Physiol, 200: 125-133). The present study was aimed at examining the involvement of Go G-proteins in rapid heterologous desensitization of native and expressed G-protein-coupled receptors in Xenopus oocytes. Threshold stimulation of the native lysophosphatidic acid receptors (LPA-Rs) induced about 50% rapid desensitization of responses evoked by stimulation of either native trypsin or expressed M1-muscarinic cholinergic receptors (M1-Rs). Similarly, threshold stimulation of expressed M1-Rs or thyrotropin-releasing hormone receptors induced 40% rapid desensitization of responses to LPA. Inactivation of all Gi/o G-proteins with pertussis toxin (PTX) completely abolished rapid heterologous desensitization in all protocols. Depletion of either Galphao or Galphao1 by antisense oligodeoxynucleotides targeted at either member of the Galphao family decreased or completely abolished rapid heterologous desensitization. Expression of two dominant negative mutants of the human Galphao family, highly homologous to oocyte Galphao species, either decreased or virtually abolished rapid desensitization. Homologous and heterologous desensitizations of the LPA response were non-additive and proceeded, apparently, via the same pathway. We conclude that Go G-proteins mediate both homologous and heterologous rapid desensitization of responses mediated by G-protein-coupled receptors (GPCRs) coupled to the phosphoinositide phospholipase C-inositol 1,4,5-trisphosphate-Ca(2+) (PI-PLC-InsP(3)-Ca(2+)) pathway in Xenopus oocytes.

show abstract

Section: Handling Of Oocytesmentioning

confidence: 99%

Section: Rapid Heterologous Desensitization Of Responses In Xenopus Omentioning

confidence: 99%

mentioning

confidence: 98%

mentioning

confidence: 99%

See 2 more Smart Citations

Go G‐proteins mediate rapid heterologous desensitization of G‐protein coupled receptors in Xenopus oocytes

Van-Ham

Oron

2005

Journal Cellular Physiology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Furthermore, the response latency provides a temporal window for integration of external signals that affect the amplitude of the response (Lipinsky et al, 1995a) and its desensitization (Lipinsky et al, 199513). The binding of guanine nucleotides to G-proteins may be affected by …”

mentioning

confidence: 99%

Alkaline pH facilitates the exchange of guanine nucleotides: A possible mechanism for modulation of the kinetics of responses mediated by guanine nucleotide-binding proteins

Lipinsky

Oron

1996

J. Cell. Physiol.

Self Cite

View full text Add to dashboard Cite

GTP gamma S1 binding experiments in a particulate preparation from Xenopus oocytes revealed two binding sites at pH = 6.9: A high affinity site (Kd = 77 +/- 4 nM) and a low affinity site (Kd = 8.74 +/- 0.05 microM). Alkaline pH (8.5) caused a significant increase in the dissociation constants of both sites (160 +/- 46 nM and 30.7 +/- 1.6 microM, respectively). In purified plasma membrane preparation, alkaline pH increased the rate of dissociation of GTP gamma S. We have previously proposed that the activation of a G-protein by the agonist-occupied receptor is rate-limiting in the kinetics of hormone-induced responses (Lipinsky et al., 1993; Pflugers Arch., 425:140-149). We have, therefore, assayed the latencies of responses evoked by TRH at different pH, in oocytes expressing the TRH receptor. A change in the medium pH was reflected by an approximately tenfold smaller change in cellular pH (pHi). Alkalinization of the medium (from pH 7.4 to 8.5) caused a shortening of latency (by 45%), whereas acidification to pH = 6.0 prolonged it (by 87%). Moreover, alkalinization decreased the latency and increased the rate of responses to microinjected GTP gamma S, but did not change the latency of responses to microinjected InsP3. These results show that activation of plasma membrane receptors coupled to G-proteins, concurrent with a change in pHi, can alter the kinetic pattern of physiological responses, thus affecting the ultimate physiological output of the cell. This finding suggests that a change of pH, is a novel potential mechanism for modulation of responses mediated by G-proteins.

show abstract

Response to lysophosphatidic acid in Xenopus oocytes and its rapid desensitization: The role of Gq and Go G‐protein families

Van-Ham

Lupu-Meiri

Tayer

et al. 2004

Journal Cellular Physiology

Self Cite

View full text Add to dashboard Cite

Native Xenopus oocytes exhibit dose-dependent depolarizing current responses to lysophosphatidic acid (LPA), with EC50 = 0.18 microM. Responses to LPA were subject to pronounced rapid desensitization. When oocytes were challenged with 5 nM LPA, the response was <10% of the maximal. Subsequent addition of 0.5 microM LPA resulted in 50-70% desensitization, when compared to naïve controls. Injection of antisense oligodeoxyoligonucleotides (ASODNs) targeted at either of the two endogenous LPA receptors inhibited the LPA response by approximately 50%, but did not alter the degree of rapid desensitization. To study the involvement of G-proteins in rapid homologous desensitization of responses to LPA, we selectively depleted native G-proteins by injection of specific ASDONs. Injection of ASDONs targeted at Galphaq family mRNAs (mainly Galpha11) reduced the response to 0.5 microM LPA by 50%. ASDONs targeted at either Galphao or Galphao1 caused a large decrease in the amount of their cognate mRNAs and the Galphao family proteins, while the response to LPA was inhibited by up to 30%. Injection of ASDONs targeted at Galphao1 mRNA decreased rapid desensitization from 69 to 23%, while pertussis toxin (PTX) completely abolished it. Expression of two dominant negative mutants of the human Galphao family homologs either decreased or virtually abolished rapid desensitization. Microinjection of CaCl(2) demonstrated that 50% of rapid desensitization could be attributed to inhibition of Ca(2+) activation of chloride channels. We propose that the apparent degenerate coupling of different G-proteins to LPA receptors in Xenopus oocytes actually serves both the generation of the response (by Gq and Go G-protein families) and its desensitization (mostly by Go G-protein family).

show abstract

Desensitization of the response to thyrotropin-releasing hormone in Xenopus oocytes is an amplified process that precedes calcium mobilization

Cited by 12 publications

References 35 publications

Go G‐proteins mediate rapid heterologous desensitization of G‐protein coupled receptors in Xenopus oocytes

Go G‐proteins mediate rapid heterologous desensitization of G‐protein coupled receptors in Xenopus oocytes

Alkaline pH facilitates the exchange of guanine nucleotides: A possible mechanism for modulation of the kinetics of responses mediated by guanine nucleotide-binding proteins

Response to lysophosphatidic acid in Xenopus oocytes and its rapid desensitization: The role of Gq and Go G‐protein families

Contact Info

Product

Resources

About