Cell Line

Neurotensin receptor 1 (NTS1) is a member of G-protein coupled receptor family A and is a receptor for Neurotensin (NT). Neurotensin (NT) exerts its intracellular effect by interacting with 3 different receptors. Two of these receptors (NTR1 and NTR2) belong to the G protein-coupled receptor family, whereas the third one (NTR3) is a type I receptor with a single transmembrane domain. The NTS1 is expressed in CNS such as cerebral cortex, basal ganglia, limbic areas, vestibular system, and esophageal smooth muscle.

Oxytocin is an abundant neuropeptide that exerts a wide spectrum of central and peripheral effects. In the context of human reproduction, oxytocin promotes uterine contractions and lactation. It is the most commonly used drug for labor induction. Oxytocin receptors are expressed in the uterus and in mammary glands, where they mediate functions related to partutition, such as contraction of the uterine myometrium during labor and milk letdown. In addition, oxytocin receptors are expressed in a variety of other peripheral tissues and in the brain, where oxytocin mediates a variety of functions. OXTR antagonists may be promising candidates to prevent preterm labor and dysmenorrheal and its agonists may also be useful for treatment of psychiatric illnesses such as anxiety, drug abuse, sexual dysfunctions, eating disorders, and autism.

Tachykinins are peptides sharing the common C-terminal amino acid sequence Phe-X-Gly-Leu-Met-NH₂. This neuropeptide family is composed of substance P, neurokinin A, and neurokinin B, which are widely distributed in mammalian central and peripheral nervous systems. It plays a role as both a neurotransmitter and a neuromodulator. Their actions are mediated by binding with three distinct receptors, namely, NK1, NK2, and NK3. NK1 has high affinity with substance P. In the CNS, NK1 has been implicated to play a role in regulating neuronal survival and degeneration. In the cardiovascular system, NK1 mediates endothelium-dependent vasodilatation and plasma protein extravasations. In the gastrointestinal system, NK1 receptors mediate intestinal motility, secretion, and vascular functions. SP-NK1 receptor communication is also involved in glioma development and progression. NK1 receptor antagonists may have several therapeutic applications in diseases mediated by tachykinins, such as

Tachykinins are peptides sharing a common C-terminal amino acid sequence: Phe-X-Gly-Leu-Met-NH₂. This neuropeptide family is composed of substance P, neurokinin A, and neurokinin B, which are widely distributed in mammalian central and peripheral nervous systems. These three molecules serve as both neurotransmitters and neuromodulators. Their actions are mediated by binding with three distinct receptors, namely NK1, NK2, and NK3. In particular, NK2 is expressed in gastrointestinal tract. Activation of NK2 is chiefly responsible for the regulation of intestinal motor functions (both excitatory and inhibitory), secretions, inflammation, and visceral sensitivity. Antagonists of NK2 may be useful in the treatment of irritable bowel syndrome.

Tachykinins are peptides sharing a common C-terminal amino acid sequence: Phe-X-Gly-Leu-Met-NH₂. This neuropeptide family is composed of substance P, neurokinin A, and neurokinin B, which are widely distributed in mammalian central and peripheral nervous systems. These three molecules serve as both neurotransmitters and neuromodulators. Their actions are mediated by binding with three distinct receptors, namely NK1, NK2, and NK3. NK3 receptors show affinity for neurokinin B. They are predominantly expressed in both the peripheral and central nervous systems. NK3 receptors appear to modulate monoaminergic and amino acid neurotransmission. Studies show that manipulating modulation of NK3 receptor activity may have therapeutic utility in psychiatric diseases such as schizophrenia and affective disorders.

Thyrtropin-releasing hormone receptor1 (TRH1) is a member of G-protein coupled receptor family A. This protein is a receptor for Thyrtropin-releasing hormone (TRH). Human TRH1 is expressed in lymphocytes, pituitary gland and CNS. It can stimulate the releasing of prolactin (PRL), thyrotropin (TSH). TRH1 receptor knockout mice exhibit a slightly reduced growth rate, considerable decrease in serum T₃, T₄, and prolactin levels but no alteration of thyroid-stimulating hormone levels.

The Vasoactive intestinal Peptide/Pituitary Adenylate Cyclase Activating Polypeptide (VPAC) receptor is G protein-coupled and has been divided into at least three types: PAC1, VPAC1, and VPAC2. High expression of PAC1 is observed in CNS and the adrenal medulla. Several splice variants of PAC1 result in proteins that differ at the N-terminus and third intracellular loop; these variants differ in their affinities for PACAP and abilities to activate Gq and Gs. This manual describes establishment of a cell line and a protocol of pharmacologically validated human PAC1 GPCR receptor (Genebank Accession Number: NM_003382).

The antidiuretic hormone arginine vasopressin (AVP) receptors are G protein-coupled receptors which consists of at least three types: V1A (vascular/hepatic) and V1B (anterior pituitary) receptors, which act through phosphatidylinositol hydrolysis to mobilize intracellular Ca²⁺; and V2 (kidney) receptor, which is coupled to adenylate cyclase. V1B receptors are expressed in anterior pituitary where they mediate the release of ACTH . Its peripheral actions, such as antidiuresis, contraction of vascular smooth muscle, and stimulation of hepatic glycogenolysis are well characterized.

Protease-activated receptor (PAR)-4 is a member of a unique family of GPCRs. The protease-activated receptors (PARs) that are activated by proteolytic cleavage of the N-terminal domain of the receptor reveal a tethered ligand. The PAR family consists of 4 receptors; PAR1 and PAR3 are activated by thrombin, and PAR2 and PAR4 are activated by several serine proteases (Macfarlane et al., 2001). PAR4 is a recently identified low-affinity thrombin receptor that plays a pathophysiological role in many types of tissues including the lung. Mice lacking PAR4 are protected from mesenteric arteriole thrombosis, indicating that PAR4 is a potential target for treatment of thrombosis in humans.