Abstract Potential G protein-coupled receptor kinase (GRK) and protein kinase A (PKA) mediation of homologous desensitization of corticotropin-releasing factor type 1 (CRF 1 ) receptors was investigated in human retinoblastoma Y-79 cells. Inhibition of PKA activity by PKI 5–22 or H-89 failed to attenuate homologous desensitization of CRF 1 receptors, and direct activation of PKA by forskolin or dibutyryl cAMP failed to desensitize CRF-induced cAMP accumulation. However, treatment of permeabilized Y-79 cells with heparin, a nonselective GRK inhibitor, reduced homologous desensitization of CRF 1 receptors by ∼35%. Furthermore, Y-79 cell uptake of a GRK3 antisense oligonucleotide (ODN), but not of a random or mismatched ODN, reduced GRK3 mRNA expression by ∼50% without altering GRK2 mRNA expression and inhibited homologous desensitization of CRF 1 receptors by ∼55%. Finally, Y-79 cells transfected with a GRK3 antisense cDNA construct exhibited an ∼50% reduction in GRK3 protein expression and an ∼65% reduction in homologous desensitization of CRF 1 receptors. We conclude that GRK3 contributes importantly to the homologous desensitization of CRF 1 receptors in Y-79 cells, a brain-derived cell line. antisense G protein-coupled receptor kinase corticotropin-releasing factor type 1 receptor regulation homologous and heterologous desensitization of the CRF 1 receptor Footnotes R. L. Hauger received support from a Veterans Affairs Merit Review grant; the VA VISN 22 Mental Illness Research, Education and Clinical Center (MIRECC); and the National Institute of Mental Health Mental Health Clinical Research Center (PHS MH-20914–14). A portion of this research received financial support from the Max Planck Institute for Experimental Medicine, Department of Molecular Neuroendocrinology (Director: Dr. Joachim Spiess), Goettingen, Germany. Address for reprint requests and other correspondence: R. L. Hauger, VA Medical Center and Dept. of Psychiatry, Univ. of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0603 (E-mail: email@example.com ). The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “ advertisement ” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Copyright © 2001 the American Physiological Society
AJP - Regulatory, Integrative and Comparative Physiology – The American Physiological Society
Published: Apr 1, 2001
It’s your single place to instantly
discover and read the research
that matters to you.
Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.
All for just $49/month
Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly
Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.
Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.
Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.
All the latest content is available, no embargo periods.
“Hi guys, I cannot tell you how much I love this resource. Incredible. I really believe you've hit the nail on the head with this site in regards to solving the research-purchase issue.”Daniel C.
“Whoa! It’s like Spotify but for academic articles.”@Phil_Robichaud
“I must say, @deepdyve is a fabulous solution to the independent researcher's problem of #access to #information.”@deepthiw
“My last article couldn't be possible without the platform @deepdyve that makes journal papers cheaper.”@JoseServera