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Titolo:
A CHIMERIC VIP-PACAP ANALOG BUT NOT VIP PSEUDOPEPTIDES FUNCTION AS VIP RECEPTOR ANTAGONISTS
Autore:
FISHBEIN VA; COY DH; HOCART SJ; JIANG NY; MROZINSKI JE; MANTEY SA; JENSEN RT;
Indirizzi:
NIDDKD,DIGEST DIS BRANCH,BLDG 10,ROOM 9C-103 BETHESDA MD 20892 NIDDKD,DIGEST DIS BRANCH BETHESDA MD 20892 TULANE UNIV,SCH MED,PEPTIDE RES LABS NEW ORLEANS LA 70112
Titolo Testata:
Peptides
fascicolo: 1, volume: 15, anno: 1994,
pagine: 95 - 100
SICI:
0196-9781(1994)15:1<95:ACVABN>2.0.ZU;2-3
Fonte:
ISI
Lingua:
ENG
Soggetto:
VASOACTIVE-INTESTINAL-PEPTIDE; HORMONE-RELEASING-FACTOR; PIG PANCREATIC ACINI; BIOLOGICAL-ACTIVITY; DISPERSED ACINI; SPINAL-CORD; SECRETIN; CELLS; BACKBONE; GALANIN;
Keywords:
RECEPTOR ANTAGONIST; SECRETIN; GROWTH HORMONE-RELEASING PEPTIDE; PSEUDOPEPTIDE; CHIMERIC PEPTIDE; PACAP;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
47
Recensione:
Indirizzi per estratti:
Citazione:
V.A. Fishbein et al., "A CHIMERIC VIP-PACAP ANALOG BUT NOT VIP PSEUDOPEPTIDES FUNCTION AS VIP RECEPTOR ANTAGONISTS", Peptides, 15(1), 1994, pp. 95-100

Abstract

The ability to assess the importance of VIP in different physiological processes is limited by the lack of specific potent antagonists. In the present study, we have adopted two different approaches used successfully with other peptides in an attempt to identify new VIP receptorantagonists. One involves the formation of pseudopeptides by insertion of reduced peptide bonds in the NH2-terminus from position 2 to 8 ofVIP. The other methodology involves the formation of a COOH-terminal chimeric analogue by combining VIP(6-28) and PACAP(28-38). The abilityof each of these peptides to function as an antagonist was compared with reported VIP antagonists. All of the peptides inhibited [I-125]VIPbinding to VIP receptors on guinea pig pancreatic acini. For the pseudopeptides the affinities were: [psi 3-4]VIP (0.2 mu M) = 4 X [psi 4-5]VIP = 8 X [psi 8-9]VIP = 14 X [psi 6-7]VIP, [psi 2-3]VIP = 25 X [psi 5-6]VIP. Each nonpseudopeptide analogue also inhibited VIP binding with relative potencies of VIP(6-28)-PACAP(28-38) (1 mu M)= 2.5 X [4-Cl-D-Phe(6),Leu(17)]VIP, VIP(10-28), neurotensin(6-11)-VIP(7-28) = 6 X [Ac-Tyr(1),D-Phe(2)]GRF. All pseudopeptides were agonists with relative potencies: [psi 3-4]VIP > [psi 6-7], [psi 4-5]VIP > [psi 5-6] > [psi 8-9]VIP > [psi 2-3]VIP. The reported VIP receptor antagonist, neurotensin(6-1l)-VIP(7-28), was also an agonist. Each of the remaining peptideshad no agonist activity; however, each inhibited VIP-stimulated amylase release with potencies of: VIP(6-28)-PACAP(28-38) = VIP(6-28) (K-i = 0.3 mu M) = 2 X [4-Cl-D-Phe(6),Leu(17)]VIP = 3 x VIP(10-28) = 9 X [Ac-Tyr(1),D-Phe(2)]GRF. We conclude that the strategy of making reducedpeptide bond analogues at the NH2-terminus of VIP does not result in receptor antagonists as it did with secretin or GRF. A chimeric analogue, VIP(6-28)-PACAP(28-38), is two times more potent than any existingVIP antagonist; however, its increase in affinity is due to the presence of the VIP(6-28) moiety entirely. This raises the possibility thatadditional, more potent, antagonists may be developed by modifying VIP(6-28).

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 07/07/20 alle ore 22:11:55