Naslov
Dipeptidyl peptidase IV (DPPIV) enzyme activity on immature T-cell line R1.1 is down-regulated by dynorphin-A(1-17) as a non-substrate inhibitor

Autori
Gabrilovac, Jelka ; Abramić, Marija ; Užarević, Branka ; Andreis, Ana ; Poljak, Ljiljana

Izvornik
Life sciences (0024-3205) 73 (2003), 2; 151-166

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Dipeptidyl peptidase IV (DPPIV); Dynorphin-A(1-17); Natural inhibitor; Kappa opioid receptor (KOR); T lymphocytes

Sažetak
Surface expression of CD26 and the corresponding enzyme activity of dipeptidyl peptidase IV (DPPIV) on the cells of immature murine T-cell line, R1.1 was examined. The data obtained have shown that R1.1 cells express high density of surface CD26 as compared to normal thymus cells. This was associated with strong enzyme activity, which, based on substrate and inhibitor specificity, corresponded to DPPIV. In addition, the effect of dynorphin-A(1-17), an endogenous opioid peptide with selectivity for kappa opioid receptors (KOR) on DPPIV of R1.1 cells was also examined. Dynorphin-A(1-17) down-regulated DPPIV in a dose-dependent manner, with the potency similar to that of substance P, a known natural DPPIV substrate. DPPIV down-regulation was resistent to bestatin and thiorphan, the inhibitors of two cell surface peptidases (APN and NEP, respectively) with potential of dynorphin-A(1-17) degradation, suggesting that the mechanism underlaying the observed effect does not involve degradative products of dynorphin-A(1-17). DPPIV down-regulation was also resistent to KOR antagonist, NBI, suggesting that the mechanism underlaying the observed phenomenon involves neither cointernalisation of KOR and DPPIV. Collectively, cells of immature murine T-cell line, R1.1 exert strong DPPIV enzyme activity, which could be down-regulated in the presence of dynorphin-A(1-17) by mechanism that presumably includes non-substrate inhibition. By down-regulating DPPIV, dynorphin-A(1-17) may indirectly affect activity and/or specificity of natural substrates of DPPIV, such as substance P, RANTES, and endomorphines.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA