Bifunctional pharmacophores. Biological activities of the peptide analog containing both casomorphine-like and substance P antagonist-like active elements.
SP-antagonistic properties of a newly synthesized peptide Tyr-Pro-D-Phe-Phe-D-Phe-D-Trp-MetNH2 (AWL-60) were investigated both in vitro and in vivo. In vitro AWL-60 effectively antagonized the action of SP-agonist (SP6-11); however, this antagonism was non-competitive. Antagonistic properties of AWL-60 were also observed in vivo: in doses as low as 0.1 nmol/kg iv AWL-60 markedly attenuated the fall in blood pressure produced by [less than Glu]6SP6-11. Since AWL-60 exerts weak opioid agonistic properties (as a casomorphine analog) the possible involvement of an opioid agonistic component in their SP inhibitory action is considered.
D000595:Amino Acid Sequence; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003432:Cross-Linking Reagents; D004723:Endorphins / Q000494:pharmacology*; D006168:Guinea Pigs; D007082:Ileum; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D008969:Molecular Sequence Data; D009130:Muscle, Smooth / Q000187:drug effects; D009842:Oligopeptides / Q000138:chemical synthesis / Q000494:pharmacology*; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D051381:Rats; D017208:Rats, Wistar; D013373:Substance P / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D003432:Cross-Linking Reagents; D004723:Endorphins; D009842:Oligopeptides; D010446:Peptide Fragments; C077812:AWL 60; D013373:Substance P; C032292:substance P (6-11); C034812:beta-casomorphin 5; D011761:Pyrrolidonecarboxylic Acid