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PMID: 8506347 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Single amino acid substitution affects desensitization of the 5-hydroxytryptamine type 3 receptor expressed in Xenopus oocytes.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 90 ·No. 11 ·1993-06-01 ·Pages 5030-3

Yakel JL, Lagrutta A, Adelman JP, North RA

Abstract

5-Hydroxytryptamine type 3 receptors were expressed in Xenopus oocytes from a cloned cDNA. The peak inward current evoked by 5-hydroxytryptamine (30 microM) was linearly related to the holding potential (-100 to +20 mV) and reversed near 0 mV. The inward current (at -60 mV) declined during the continued presence of 5-hydroxytryptamine with a half-time of about 2 s; this desensitization was 20 times slower in calcium-free solution. Desensitization was markedly different in channels in which Leu286 was changed by site-directed mutagenesis; this residue is thought to lie near the middle of the M2 segment. Desensitization was faster with Phe, Tyr, or Ala in this position and slower with Thr. Phe and Thr substitutions in the equivalent position of the nicotinic acetylcholine receptor have similar effects on desensitization, suggesting that the underlying conformational change might be common to ligand-gated channels.

MeSH Terms
Amino Acid Sequence Animals Chelating Agents/pharmacology Clone Cells Dose-Response Relationship, Drug Egtazic Acid/analogs & derivatives,pharmacology Female Leucine Membrane Potentials/drug effects Mutagenesis, Site-Directed Oocytes/drug effects,physiology Receptors, Serotonin/drug effects,genetics,physiology Sequence Homology, Amino Acid Serotonin/pharmacology Xenopus laevis
Chemicals
Chelating Agents Receptors, Serotonin Serotonin Egtazic Acid Leucine 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Yakel J L
Vollum Institute, Oregon Health Sciences University, Portland 97201.
Lagrutta A
Adelman J P
North R A
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.90.11.5030
Published
1993-06-01
Pages
5030-3
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC46647
Subset
IM
Grants
NIDA NIH HHS · DA03160 · United States
NINDS NIH HHS · NS28504 · United States
External Links
PubMed source DOI: 10.1073/pnas.90.11.5030 PMC Full Text View journal details
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