title: Heterologous desensitization of the human endothelin A and neurokinin A receptors in Xenopus laevis oocytes.
abstract: Endothelin 1 (ET1) desensitizes endothelin A receptor for 90-110 min while neurokinin A (NKA) desensitizes neurokinin A receptor for 25-35 min in Xenopus laevis oocytes. In the present study, endothelin A receptor and neurokinin A receptor were coexpressed in Xenopus laevis oocytes in an effort to characterize heterologous desensitization of the receptors that activate phospholipase C-beta. ET1 desensitizes both the endothelin A receptor and the neurokinin A receptor for 90-110 min, whereas stimulation with NKA desensitizes the same two receptors for only 25-35 min. Homologous and heterologous desensitization experiments were also carried out with endothelin 3 (ET3), a ligand that exhibits lower affinity to the endothelin A receptor and a quicker dissociation rate than ET1. ET3 was unable to desensitize endothelin A receptor and the neurokinin A receptor; this is in contrast to ET1 that desensitizes both receptors. These results suggests that the receptors that undergo homologous desensitization are able to heterologously desensitize other receptors that activate PLC-beta. Furthermore, the agonist-specific dissociation constant dictates the extent of desensitization and time of recovery of the receptor-mediated response.
authors.affiliation: Department of Pharmacology, New York University Medical Center, New York University School of Medicine, NY 10016, USA.
authors.forename: C R
authors.initials: CR
authors.lastname: Cyr
authors.forename: L A
authors.initials: LA
authors.lastname: Devi
authors.forename: B
authors.initials: B
authors.lastname: Rudy
authors.forename: R M
authors.initials: RM
authors.lastname: Kris
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019332:Endothelin-1 / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D015288:Neurokinin A / Q000494:pharmacology*; D009865:Oocytes; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin / Q000819:agonists / Q000187:drug effects* / Q000235:genetics; D018041:Receptors, Neurokinin-2 / Q000819:agonists / Q000187:drug effects* / Q000235:genetics; D011994:Recombinant Proteins / Q000187:drug effects; D015398:Signal Transduction; D013997:Time Factors; D014981:Xenopus
chemical_list: D019332:Endothelin-1; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin; D018041:Receptors, Neurokinin-2; D011994:Recombinant Proteins; D015288:Neurokinin A; D019204:GTP-Binding Proteins