N-terminal truncated analogs of men 10376 as tachykinin NK-2 receptor antagonists.
Three N-terminal fragments of the selective tachykinin NK-2 receptor antagonist MEN 10376 (H-Asp-Tyr-DTrp-Val-DTrp-DTrp-Lys-NH2) have been synthesized and tested in several mammalian tissues in order to establish the minimum length of the peptide chain for maintenance of the antagonist activity. Biological activity has been determined on the rabbit pulmonary artery (RPA) and hamster trachea (HT) preparations, chosen as representative of the NK-2A and NK-2B receptor subtypes, respectively, and on the rabbit bronchus (RB), guinea-pig bronchus (GPB), human urinary bladder (HuUB), human ileum (HuI) and human colon (HuC) preparations to verify the previously described NK-2A character of these tissues. The N-terminal tetrapeptide was inactive in the RPA and HT, while the N-terminal hexa- and penta- peptides maintained antagonist activity in all preparation investigated. The selectivity of the latter two peptides confirms that the receptor expressed in RB, GPB, HuUB, HuC and HuI tissues is of the NK-2A type.
Quartara
L
L
Chemistry Department, A. Menarini Pharmaceuticals, Firenze, Italy.
Patacchini
R
R
Giuliani
S
S
Renzetti
A R
AR
Rovero
P
P
Maggi
C A
CA
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism; D001980:Bronchi / Q000378:metabolism; D006224:Cricetinae; D006168:Guinea Pigs; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D008969:Molecular Sequence Data; D015288:Neurokinin A / Q000031:analogs & derivatives* / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000187:drug effects; D011817:Rabbits; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors*; D018039:Receptors, Tachykinin; D013329:Structure-Activity Relationship; D015320:Tachykinins / Q000037:antagonists & inhibitors; D014132:Trachea / Q000378:metabolism
D009842:Oligopeptides; D010446:Peptide Fragments; D017981:Receptors, Neurotransmitter; D018039:Receptors, Tachykinin; D015320:Tachykinins; C069192:neurokinin A(4-10), Tyr(5)-Trp(6,8,9)-Lys(10)-; D015288:Neurokinin A