PT  - JOURNAL ARTICLE
AU  - Mark A. Simmons
TI  - Functional Selectivity of NK<sub>1</sub> Receptor Signaling: Peptide Agonists Can Preferentially Produce Receptor Activation or Desensitization
AID  - 10.1124/jpet.106.109512
DP  - 2006 Nov 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 907--913
VI  - 319
IP  - 2
4099  - http://jpet.aspetjournals.org/content/319/2/907.short
4100  - http://jpet.aspetjournals.org/content/319/2/907.full
SO  - J Pharmacol Exp Ther2006 Nov 01; 319
AB  - A cascade of events follows binding of an agonist ligand to the tachykinin NK1 receptor. These events include activation of multiple signal transduction pathways as well as cellular modulation of receptor function by the process of desensitization. This study examines the differences in the abilities of naturally occurring peptide agonist ligands of the tachykinin NK1 receptor to preferentially direct signaling through the receptor to produce signal activation versus receptor desensitization. The differential effects of tachykinin peptides with respect to ligand competition binding, receptor-G protein coupling, intracellular Ca2+ elevations, and receptor desensitization have been measured. In relation to its potency in competition binding studies, substance P produces desensitization at lower concentrations, whereas higher concentrations are required to elicit a Ca2+ response. In contrast to this, a related peptide, ranatachykinin C, is more effective at activating a Ca2+ response relative to its ability to produce desensitization. This difference in functional selectivity is conserved for an amphibian and two mammalian ortholog tachykinin receptors. The present study demonstrates that peptide agonist ligands of NK1 receptors can preferentially produce signal activation or desensitization. The American Society for Pharmacology and Experimental Therapeutics