Tachykinin GPCR Assays
Background of Tachykinin Receptors
NK1, NK2, and NK3 receptors are a group of tachykinin G protein-coupled receptors, activated by over 40 tachykinin peptide ligands, including neurokinin A, neurokinin B, and substance P. Those ligands have a common C-terminal sequence Phe-X- Gly-Leu-Met.
Fig.1 Crystal structure of the Neurokinin 1 receptor in complex with the small molecule antagonist CP 999940. (Barrett, 2019)
Distributions and Functions of Tachykinin Receptors
NK1 receptors are broadly present in the central nervous system and peripheral tissues, such as the hypothalamus, frontal cortex, sensorimotor cortex, and gastrointestinal tract. NK1 receptors are involved in emotional processes in the central nervous system and visceral pain sensitivity. The antagonists of NK1 receptors are capable of treating psychological disorders and preventing infection and inflammation for irritable bowel syndrome and asthma. NK2 receptors are primarily distributed in the smooth muscle of the gastrointestinal tract, respiratory tract, and urinary tract. NK2 receptors participate in smooth muscle contraction and relaxation, vasodilation, activation of the immune system, regulation of visceral pain sensitivity, and the regulation of gastrointestinal motility. The antagonists of NK2 receptors are used as anti-depressants and treatments for irritable bowel syndrome. The distribution of NK3 receptors is similar to NK1 receptors. They play important roles in multiple pathological and physiological processes, including obstructive airway disease, hypertension, pre-eclampsia, irritable bowel syndrome, pain perception, schizophrenia, and anxiety and depression.
Subtypes and Mechanisms of Tachykinin Receptors
The tachykinin receptors are a family of G protein-coupled receptors, including three subtypes, NK1, NK2, and NK3 receptors. The signal transduction is mediated by Gs proteins and Gq/G11 proteins.
| Receptor | Gene | Mechanism | Agonists | Antagonists |
| NK1 receptor | TACR1 |
|
|
|
| NK2 receptor | TACR2 |
|
|
|
| NK3 receptor | TACR3 |
|
|
|
Assay List of Tachykinin Receptors
Creative Biolabs can provide a range of assays of tachykinin receptors. You can choose the assay in the list or contact us for more information:
| Assay No. | Assay Name | Host Cell | Assay Type | Datasheet |
|---|---|---|---|---|
| Calcium Flux Assay | ||||
| S01YF-0722-KX200 | Magic™ Human TACR3 In Vitro Calcium Assay, HEK293-Ga15 | HEK293-Ga15 | Calcium Flux Assay | |
Published Data
| Paper Title | In vitro and in vivo pharmacological characterization of the novel NK1 receptor selective antagonist Netupitant. |
| Journal | Peptides |
| Published | 2012 |
| Abstract | The study aimed to investigate the in vitro and in vivo pharmacological characterization of the novel NK1 receptor ligand Netupitant. In vitro studies used recombinant human and rat NK receptors stably expressed in CHO and HEK293 cells. Then intracellular calcium concentrations were measured. SP-induced contractions were measured at native guinea pig NK1 receptors expressed in the ileum. The in vivo scratching, biting, and licking (SBL) test was performed in mice. In addition, they used foot tapping assay in gerbils. Netupitant can be a potent and selective NK1 antagonist and be useful in the control of central and peripheral functions for treating patients with chemotherapy-induced nausea and vomiting. |
| Result |
CHO cells expressing the human NK receptors responded to a panel of agonists, which showed the expected order of potency in calcium mobilization studies. In CHO NK1 cells, Netupitant concentration-dependently antagonized the stimulatory effects of substance P (SP) with insurmountable antagonism of pKB 8.87, while Netupitant showed no activity in cells expressing NK2 or NK3 receptors. In the guinea pig ileum, Netupitant concentration dependently depressed the maximal response to SP with pKB 7.85. The result of functional washout experiments displayed persistent (up to 5 h) antagonist effects. The intrathecal injection of SP elicited the typical scratching, biting, and licking response in mice with dose-dependently inhibition of Netupitant. Foot tapping behavior of gerbils evoked by the dose-dependent intracerebroventricular injection of Netupitant given intraperitoneally (ID50 1.5 mg/kg) or orally (ID50 0.5 mg/kg). In all the assays Aprepitant elicited similar effects as Netupitant, suggesting that Netupitant may exert as a brain penetrant, orally active, potent, and selective NK1 antagonist.
|
Fig.2 Inhibition-response curves to NK receptor antagonists and the stimulatory effect of a fixed concentration of agonist in CHO cells expressing the human NK1, NK2, and NK3 receptors using calcium mobilization experiments. (Rizzi, 2012)
References
- Barrett J.; et al. Tachykinin receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database. IUPHAR/BPS Guide to Pharmacology CITE. 2019, 2019(4).
- Rizzi, A.; et al. In vitro and in vivo pharmacological characterization of the novel NK1 receptor selective antagonist Netupitant. Peptides. 2012, 37(1): 86-97.
