The hemispheric functional expression of the thyrotropin-releasing-hormone receptor is not determined by the receptors' physical distribution.
The thyrotropin-releasing-hormone receptor (TRH-R) is a member of a family of the G-protein-coupled receptors that share structural similarities and exert their physiological action via the inositol lipid signal-transduction pathway. The TRH-R when expressed in Xenopus oocytes exhibits marked preference of the response (increased chloride conductance) for the animal hemisphere. Whereas the rat TRH-R functional distribution was strongly asymmetric (animal/vegetal ratio = 9.5), the mouse TRH-R exhibited a significantly lower ratio (3.9). Truncation of the last 59 amino acids of the C-terminal region of the mouse TRH-R did not lead to any changes in the functional hemispheric distribution. Despite the polarization of response, receptor number was similar on both hemispheres. Moreover, the apparent half-life of the functional expression of the TRH-R was approx. 4 h on both hemispheres when the expression was inhibited by a specific antisense oligonucleotide. Inhibition of total protein synthesis with cycloheximide affected hemispheric responses mediated by each of the three TRH-Rs tested in a qualitatively different way. These results suggest that an additional, rapidly degraded, protein modulates the functional hemispheric expression of the TRH-Rs.
Matus-Leibovitch
N
N
Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel-Aviv University, Ramat-Aviv, Israel.
Nussenzveig
D R
DR
Gershengorn
M C
MC
Oron
Y
Y
D000818:Animals; D003513:Cycloheximide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D051379:Mice; D016297:Mutagenesis, Site-Directed; D016376:Oligonucleotides, Antisense / Q000378:metabolism / Q000494:pharmacology; D009865:Oocytes / Q000187:drug effects / Q000502:physiology*; D010911:Pituitary Neoplasms / Q000378:metabolism; D017354:Point Mutation; D012313:RNA / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism; D051381:Rats; D018025:Receptors, Thyrotropin-Releasing Hormone / Q000096:biosynthesis*; D013045:Species Specificity; D014981:Xenopus
D016376:Oligonucleotides, Antisense; D012334:RNA, Neoplasm; D018025:Receptors, Thyrotropin-Releasing Hormone; D012313:RNA; D003513:Cycloheximide; D019204:GTP-Binding Proteins