Comparison of G-protein selectivity of human 5-HT2C and 5-HT1A receptors

Mitsuko Okada, David Goldman, Markku Linnoila, Nakao Iwata, Norio Ozaki, John K. Northup

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

We compared the ability of human 5-HT2C and 5-HT1A receptors to couple to selected G proteins expressed in insect Sf9 cells through simultaneous infection with recombinant baculoviruses. We also examined the coupling of G proteins to these same receptors in membranes derived from the Sf9 cells using in situ reconstitution with purified G proteins. Our data show that unoccupied 5-HT2C and 5-HT1A receptors can attain an activated conformation that is stabilized by interaction with specific G proteins. While high-affinity agonist binding to the 5-HT2C receptor was increased to a greater extent by Gαq than by Gαi2, the high-affinity agonist binding to the 5-HT 1A receptor was preferentially enhanced by Gαi2 coexpression. When the two 5-HT receptors were expressed in cells also expressing G proteins, both 5-HT2C and 5-HT1A receptors appear to activate Gαi2 in preference to Gαq. In contrast, in situ reconstitution data show that 5-HT2C receptors robustly activate Gαq and marginally activate Gαo or Gαi, whereas 5-HT1A receptors only marginally activate Gαq and robustly activate Gαo and Gαi. These results suggest that the overexpression of receptor and potential G-protein coupling partners in Sf9 cells may lead to erroneous conclusions as to the signaling selectivity of receptors.

Original languageEnglish
Pages (from-to)570-577
Number of pages8
JournalAnnals of the New York Academy of Sciences
Volume1025
DOIs
Publication statusPublished - 01-01-2004

Fingerprint

Receptor, Serotonin, 5-HT1A
GTP-Binding Proteins
Sf9 Cells
Receptor, Serotonin, 5-HT2C
Baculoviridae
Serotonin Receptors
Insects
Conformations
Protein
Membranes
Cells
Infection

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

Cite this

Okada, Mitsuko ; Goldman, David ; Linnoila, Markku ; Iwata, Nakao ; Ozaki, Norio ; Northup, John K. / Comparison of G-protein selectivity of human 5-HT2C and 5-HT1A receptors. In: Annals of the New York Academy of Sciences. 2004 ; Vol. 1025. pp. 570-577.
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Comparison of G-protein selectivity of human 5-HT2C and 5-HT1A receptors. / Okada, Mitsuko; Goldman, David; Linnoila, Markku; Iwata, Nakao; Ozaki, Norio; Northup, John K.

In: Annals of the New York Academy of Sciences, Vol. 1025, 01.01.2004, p. 570-577.

Research output: Contribution to journalArticle

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T1 - Comparison of G-protein selectivity of human 5-HT2C and 5-HT1A receptors

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AU - Goldman, David

AU - Linnoila, Markku

AU - Iwata, Nakao

AU - Ozaki, Norio

AU - Northup, John K.

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