Differential activation of intracellular effector by two isoforms of human neurokinin-1 receptor.
Two isoforms of the human neurokinin-1 receptor were cloned and characterized in heterologous expression systems of mammalian cell culture and Xenopus oocytes. The two isoforms differ only in the length of the encoded polypeptide. The peptide-binding properties of the long form of human neurokinin-1 receptor are consistent with those of the native neurokinin-1 receptor of mammalian tissues, where substance P is the most potent agonist. Peptide agonists elicit an oscillating current in Xenopus oocytes expressing the long form. In contrast, the short form of human neurokinin-1 receptor expressed in COS cells binds substance P with an apparent affinity at least 10-fold lower than that of the long form, and it elicits the electrophysiological response only weakly in Xenopus oocytes. These data suggest that the short form couples to a different effector system. Sequence analysis suggested that the two isoforms may arise from alternative pre-mRNA splicing. These results indicate that multiple forms of the human neurokinin-1 receptor exist and the differential activation of intracellular effector may be involved in generating the complex biological effects of substance P.
Fong
T M
TM
Department of Molecular Pharmacology and Biochemistry, Merck Sharp & Dohme Research Laboratories, Rayway, New Jersey 07065.
Anderson
S A
SA
Yu
H
H
Huang
R R
RR
Strader
C D
CD
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D019204:GTP-Binding Proteins / Q000502:physiology; D015870:Gene Expression / Q000502:physiology; D005910:Glioma / Q000737:chemistry / Q000235:genetics; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D008969:Molecular Sequence Data; D009865:Oocytes / Q000378:metabolism / Q000502:physiology; D051381:Rats; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014162:Transfection; D014407:Tumor Cells, Cultured; D014982:Xenopus laevis
D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter; D004247:DNA; D019204:GTP-Binding Proteins