Tachykinin receptor subtypes

Three tachykinin GPCRs, NK, NK, and NK, have been identified and cloned. AH are coupled to phosphatidjhnositol hydrolysis. The NK receptor is selective for substance P (SP) and is relatively abundant in the brain, spinal cord, and peripheral tissues. The NK receptor is selective for NKA and is present in the gastrointestinal tract, urinary bladder, and adrenal gland but is low or absent in the CNS. The NIC receptor is selective for NKB and is present in low amounts in the gastrointestinal tract and urinary bladder, but is abundant in some areas of the CNS, ie, the spinal dorsal bom, soUtary nucleus, and laminae IV and V of the cortex with moderate amounts in the interpeduncular nucleus. Mismatches in the distribution of the tachykinins and tachykinin receptors suggest the possibility of additional tachykinin receptor subtypes. 

The actions of substance P and neurokinins A and are mediated by three G protein-coupled tachykinin receptors designated NK i, NK 2, and NK 3. Substance P is the preferred ligand for the NK receptor, the predominant tachykinin receptor in the human brain. However, neurokinins A and also possess considerable affinity for this receptor. In humans, most of the central and peripheral effects of substance P are mediated by NKi receptors. All three receptor subtypes are coupled to inositol trisphosphate synthesis and calcium mobilization. 

The tachykinin receptors on guinea-pig alveolar macro-ph s appear to be of the Nk2 receptor subtype. NkA is the most potent of the endogenous tachykinins in eliciting release of superoxide anion from these cells, and Nk2 selective antagonists inhibit this release (Bowden et al., 1994). 

CP 96345 is a substituted quinuclidine, a substituted isoindole, a TACHYKININ RECEPTOR ANTAGONIST selective for the NK,-receptor subtype. It also has ion channel-blocking properties, and is used as a pharmacological tool. 

It may also have ANTIPSYCHOTIC activity, dapiprazole hydrochloride dapiprazole. dapitant [inn] (RPR 100893) is a substituted isoindole, a TACHYKININ RECEPTOR ANTAGONIST, selective for the NK,-receptor subtype. It has potential as an ANTIMIGRAINE AGENT, dapsone [ban, inn, usan] is a sulphone with actions similar to SULPHONAMIDES and with ANTIBACTERIAL activity. It can be used as an antileprotic and for infective dermatitis herpetiformis. and is being investigated for the treatment and prevention of Pneumocystis carinii pneumonia (e.g. in AIDS), daptomycin [ban, inn, usan] is an (aminoglycoside) antibiotic. It has antibacterial properties. 

OSalmid [inn, jan] (L171 8 and many other names) is a benzamide and has been used as a CHOLERETIC AGENT, osanetant [inn] (SR 142801) is a substituted piperidinyl-methylacetamide. a TACHYKININ RECEPTOR ANTAGONIST selective for the NKs-receptor subtype. 

FUT-187) is a naphthalenyllmidazolylaminobenzoate, an ENZYME INHIBITOR active as a (serine) PROTEASE INHIBITOR. It can be used as a proteolysis inhibitor in the treatment of postgastrectoiTty reflux oesophagitis, sepimostat methanesulfonate sepimostat. septide ([pGlu Pro ] Pe.n) is a substance P derivative, a TACHYKININ RECEPTOR AGONIST, selective at the NK -receptor subtype. It is used as a pharmacological tool. 

Maggi, C.A. (1994) Evidence for receptor subtypes/species variants of receptors, in The Tachykinin Receptors, (ed. S.H. Buck). Humana Press. Totowa. NJ.pp. 395-470. 

---