Tachykinin receptors

SP > NKA > NKB SP methyl ester

Potency order

Selective agonists

human P25103 7TM 407 aa rat 1~146007TM

K

B

lP,/DG rtkr 468 aa human P2Y371 7TM 452 aa rat 1’2~0537TM

skr 398 aa human 1’21452 7TM 390 aa rat PlhbfO 7TM 384 aa bovine ~05363 7TM

[BH]senktide [ W1BH-elcdoisin 1W]-/MePheT]NKB

(agtrnist at other t,lchykinin wccptuw)

[Trp7,~-Ala~jNKA~_~~~

1l’W]NK.B

senktide iMePhe7JNK~

NKB > NKA > SP

SF-N / W-E, ncurokinin

NK3

lP,/DG

[SHJNKA (125l]iodohistidyl-NKA

SR48968 (8.0-10.0) GR94800 (9.6) L659877 (6.9-7.9)

[j3-Alan]NKA4-,<, CR64349 [Lys’,MeLeuq,NlelL’]NKAJ-l(r

NKA P NKB >> SP

W-E / SI’-K, substance

NM2

*nomenclature as agreed

in the Symposium ‘Substance P and Neurokinins - Montreal 19%

Endogenous ligands: substance P (SP), neur~kinjn A (NKA, previous names substance K, fl~urokinin cr,neuromedin L), neurokinin neurokinin p, neuromedin K), neuropeptide K and neuropeptide y (N-terminally extended forms of neurokinin A)

B (NKE; prc~iousnames

Other ~ece~tors/binding sites: Species homolo~ues of the NK, receptor exist; the antagonists CP99Y94 and CP96345 are selective for human and ~u~t~ea-~i~ whereas the antagonist RP67580 is selective for rat and mouse. Species homologues of the NK, receptor exist: the potency order of NKI antagonists in some species, e.g. rabbit (MEN10207 > L659877 > R39h), differs from that in others, e.g. hamster (LhSY877 > R396 > MEN10207). Functional and binding studies indicate the presence of novel receptors in bovine adrenal medulla and in the CNS that recognize substance I’,_?and certain other N-terminal analogues. These are not tachykinin receptors since activity is dependent on the nonconserved N-terminal region of substance I?

Structural information

407 aa

lP,/DG

Predominant effectors

Gene

[“HI- or [I?sIlBH-[Sar‘J,Met(Q)~1]SP [“HI-[Pro’]SP [“HI- or [‘2sI]BH-SF

RP67580 (7.0-9.0) CR82334 (7.2-7.6)

cp99994 (& = o.%M)

Radioligands

Selective antagonists

W-l? substance P

Previous names

[Sar’?Met(Oz)~‘]SP [ Pro’]SP

NKI

Nomenclature*