An approach to the elucidation of self-regulatory mechanism of substance P action. I. Synthesis and biological properties of pentapeptides related both to the substance P C-terminal fragment and enkephalins.
Seven pentapeptides, chemically related both to C-terminal fragment of substance P and Met-enkephalin were synthetized and their pharmacological properties were investigated. Peptides I-VI (L-amino acid residue in position 2) antagonized the inhibitory action of D-Ala2-Met-EK-NH2 on isolated vas deferens in vitro but were devoid of opiate-receptor binding activity in radioreceptor studies. Peptide VII (D-Phe2-Met-EK-NH2) exerted a weak inhibitory effect on contractions of transmurally stimulated vas deferens of rat which was abolished by naloxone (10(-8) M) and showed relatively strong but short-lasting analgesic activity in vivo. This peptide at concentration above 10(-5) M partially displaced the 3H-naloxone from its binding sites in striatal membranes. The possible existence of the neuronal substance P-enkephalin self-regulatory mechanism is discussed.
D000595:Amino Acid Sequence; D000700:Analgesics; D000818:Animals; D004745:Enkephalins / Q000138:chemical synthesis / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D018377:Neurotransmitter Agents / Q000502:physiology; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D013373:Substance P / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology*
D000700:Analgesics; D004745:Enkephalins; D018377:Neurotransmitter Agents; D010446:Peptide Fragments; D013373:Substance P