TY - JOUR T1 - Differential activation of intracellular effector by two isoforms of human neurokinin-1 receptor. JF - Molecular Pharmacology JO - Mol Pharmacol SP - 24 LP - 30 VL - 41 IS - 1 AU - T M Fong AU - S A Anderson AU - H Yu AU - R R Huang AU - C D Strader Y1 - 1992/01/01 UR - http://molpharm.aspetjournals.org/content/41/1/24.abstract N2 - 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. ER -