Affinity of R 396, an NK-2 tachykinin receptor antagonist, for NK-2 receptors in preparations from different species.
We have assessed the affinity of R 396 (Ac. Leu-Asp-Gln-Trp-Phe-Gly NH2) in a number of NK-2 tachykinin receptor bearing-tissues from several species. The cyclic analog of R 396, (MEN 10354) was less potent and selective than the linear hexapeptide at NK-2 tachykinin receptors subtypes in the rabbit pulmonary artery and hamster trachea. The affinity of R 396, as measured by a smooth muscle contraction assay and a radioligand binding assay, was higher (about 10 fold) for NK-2 receptors expressed in hamster tissues (urinary bladder, stomach and trachea) than in rat tissues (urinary bladder, vas deferens, colon and stomach) and a further drop in affinity was observed in bovine tissues (urinary bladder and stomach) or rabbit bronchus. The results are discussed in relation to the proposed existence of NK-2 receptor subtypes and raise the question of the existence of species-related differences as compared to the existence of true receptor subtypes.
Maggi
C A
CA
Pharmacology Department, A. Menarini Pharmaceuticals, Florence, Italy.
Patacchini
R
R
Astolfi
M
M
Rovero
P
P
Giachetti
A
A
Van Giersbergen
P L
PL
D000595:Amino Acid Sequence; D000818:Animals; D006224:Cricetinae; D008297:Male; D008647:Mesocricetus; D008969:Molecular Sequence Data; D015288:Neurokinin A / Q000378:metabolism; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000378:metabolism*; D011817:Rabbits; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018039:Receptors, Tachykinin; D013045:Species Specificity; D015320:Tachykinins / Q000378:metabolism*
D009842:Oligopeptides; D010456:Peptides, Cyclic; D017981:Receptors, Neurotransmitter; D018039:Receptors, Tachykinin; D015320:Tachykinins; C076938:R 396; C076939:MEN 10354; D015288:Neurokinin A