Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Agonist activity of the delta-antagonists TIPP and TIPP-psi in cellular models expressing endogenous or transfected delta-opioid receptors
Autore:
Martin, NA; Terruso, MT; Prather, PL;
Indirizzi:
Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, Little Rock, AR 72205 USAUniv Arkansas Med Sci Little Rock AR USA 72205 Little Rock, AR 72205 USA
Titolo Testata:
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
fascicolo: 1, volume: 298, anno: 2001,
pagine: 240 - 248
SICI:
0022-3565(200107)298:1<240:AAOTDT>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
NG108-15 HYBRID-CELLS; ADENYLYL-CYCLASE; SIGNAL-TRANSDUCTION; MORPHINE-TOLERANCE; G-PROTEINS; BINDING; INHIBITION; NALTRINDOLE; DEPENDENCE; TIPP;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
42
Recensione:
Indirizzi per estratti:
Indirizzo: Prather, PL Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, Mail Slot 611,4301 W Markham St, Little Rock, AR 72205 USA Univ Arkansas Med Sci Mail Slot 611,4301 W Markham St Little Rock AR USA 72205
Citazione:
N.A. Martin et al., "Agonist activity of the delta-antagonists TIPP and TIPP-psi in cellular models expressing endogenous or transfected delta-opioid receptors", J PHARM EXP, 298(1), 2001, pp. 240-248

Abstract

A new class of highly selective delta -opioid receptor antagonists has been recently developed, termed the TIP(P) peptides, Two prototypical compounds in this class are TIPP (H-Tyr-Tic-Phe-Phe-OH) and a derivative, TIPP-psi (H-Tyr-Tic[CH2NH]-Phe-Phe-OH). Surprisingly, both TIPP and TIPP-psi demonstrated inhibition of adenylyl cyclase activity in GH(3) cells transfected with delta -opioid receptors (GH(3)DORT), an effect normally observed by agonists. The agonist activity was delta -selective, because no inhibition occurred in wild-type GH(3) or GH(3)MOR (mu -opioid receptor) cells. Both TIPP and TIPP-psi exhibited concentration-dependent inhibition of adenylyl cyclase activity; however, TIPP-psi was found to be less potent (IC50 = 3.97 versus 0.162 nM) and less efficacious (I-max = 50% versus 70%) than TIPP. Pretreatment of cells with pertussis toxin attenuated the inhibition of maximally effective concentrations of TIPP and TIPP-psi, indicating the involvement of G(l alpha)G(o alpha) G-proteins, Other delta -antagonists, naltriben, naloxone, and ICI 174864, attenuated the inhibition of adenylyl cyclase activity mediated by TIPP. Coadministration. of TIPP with the selective S-agonist [D-Pen(2,5)]enkephalin resulted in an additive interaction. Both TIPP and TIPP-psi exhibited significant inhibition of adenylyl cyclase activity in different GH(3)DORT clones expressing a 28-fold range of delta -opioid receptor densities, and in cell lines expressing endogenous (i.e., N1E115 andNG108-15) and transfected (i.e., Chinese hamster ovary-DOR and human embryonic kidney-DOR) delta -opioid receptors, with densities ranging from 0.12 to 6.67 pmol/mg, These results suggest that compounds previously thought tobe purely delta -opioid receptor antagonists also demonstrate agonist activity in several in vitro models.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/04/20 alle ore 02:42:40