The tachykinin peptides constitute one of the largest peptide families. To date, more than 40 tachykinins have been identified from invertebrate and vertebrate species. In mammals, three prototypical tachykinins have been isolated from neuronal tissue: substance P, neurokinin A and neurokinin B. Recently hemokinin-1 has been isolated from murine blood cells and identified as a new endogenous tachykinin. Three main tachykinin receptor types have been identified: NK1, NK2 and NK3 receptors.
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Written by Sonia Tucci, Lynsay Kobelis and Tim Kirkham, this review provides a synopsis of the increasing number of peptides that have been implicated in appetite regulation and energy homeostasis; putative roles of the major peptides are outlined and compounds available from Tocris are listed.
Major depressive disorder is characterized by depressed mood and a loss of interest and/or pleasure. Updated in 2015 this poster highlights presynaptic and postsynaptic targets for the potential treatment of major depressive disorder, as well as outlining the pharmacology of currently approved antidepressant drugs.
Schizophrenia is a debilitating psychiatric disorder that affects 1% of the worldwide population. This poster describes the neurobiology of Schizophrenia, as well as highlighting the genetic and environmental factors that play a fundamental role in the etiology of the disease. The current and emerging drug targets are also discussed.
Receptor Subtype | NK1 | NK2 | NK3 |
---|---|---|---|
Transduction Mechanism | Activates Gq/11 | Activates Gq/11 | Activates Gq/11 |
Localization | CNS (particularly the striatum, amygdala and some hypothalamic and thalamic nuclei), peripheral tissues | Periphery (inflammatory cells and bronchial, gastrointestinal and urinary smooth muscle), limited expression in the CNS | CNS (hippocampus, hypothalamus, substantia nigra, dorsal horn of the spinal cord), limited expression in the periphery |
Preferred Endogenous Ligand | Substance P (1156) > Neurokinin A (1152) > Neurokinin B (1582) | Neurokinin A (1152) > Neurokinin B (1582) > Substance P (1156) | Neurokinin B (1582) > Neurokinin A (1152) > Substance P (1156) |
Selective Agonists |
GR 73632 (1669) Hemokinin-1 (mouse) (1535) [Sar9,Met(O2)11]-Substance P (1178) Hemokinin-1 (human) (2576) |
GR 64349 (1668) [bAla8]-Neurokinin A(4-10) (1640) [Lys5,MeLeu9,Nle10]-NKA(4-10) (3228) |
Senktide (1068) |
Selective Antagonists |
FK 888 (2400) GR 82334 (1670) L-732,138 (0868) L-733,060 (1145) RP 67580 (1635) SDZ NKT 343 (2394) |
GR 159897 (1274) MDL 29,913 (1194) MEN 10376 (1632) MEN 10627 |
SB 218795 (1376) SB 222200 (1393) |