RT Journal Article
SR Electronic
T1 Differential activation of intracellular effector by two isoforms of human neurokinin-1 receptor.
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 24
OP 30
VO 41
IS 1
A1 T M Fong
A1 S A Anderson
A1 H Yu
A1 R R Huang
A1 C D Strader
YR 1992
UL http://molpharm.aspetjournals.org/content/41/1/24.abstract
AB 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.