Tissue distribution in mice of BPP 10c, a potent proline-rich anti-hypertensive peptide of Bothrops jararaca.
The snake venom proline-rich peptide BPP 10c is an active somatic angiotensin-converting enzyme (sACE) inhibitors. Recently we demonstrated that the anti-hypertensive effect of BPP 10c is not related to the inhibition of sACE alone, thus suggesting that this enzyme is not its only target for blood pressure reduction. In the present work, a biodistribution study in Swiss mice of [(125)I]-BPP 10c in the absence or in the presence of a saturating concentration of captopril, a selective active-site inhibitor of sACE, demonstrated that: (1) [(125)I]-BPP 10c was present in several organs and the renal absorption was significantly high; (2) [(125)I]-BPP 10c showed a clear preference for the kidney, maintaining a high concentration in this organ in the presence of captopril for at least 3h; (3) The residual amount of [(125)I]-BPP 10c in the kidney of animals simultaneously treated with captopril suggest that the peptide can interact with other targets different from sACE in this organ. We also showed that Cy3-labeled BPP 10c was internalized by human embryonic kidney cells (HEK-293T). Taken together, these results suggest that sACE inhibition by captopril affects the tissue distribution of [(125)I]-BPP 10c and that the anti-hypertensive effects of BPP 10c are not only dependent on sACE inhibition.
Silva
Carlos A
CA
Center for Applied Toxinology CAT-CEPID, Instituto Butantan, Av. Vital Brasil 1500, 05503-900 São Paulo, SP, Brazil.
Portaro
Fernanda C V
FC
Fernandes
Beatriz L
BL
Ianzer
Danielle A
DA
Guerreiro
Juliano R
JR
Gomes
Claudiana L
CL
Konno
Katsuhiro
K
Serrano
Solange M T
SM
Nascimento
Nanci
N
Camargo
Antonio C M
AC
D000818:Animals; D000959:Antihypertensive Agents / Q000737:chemistry / Q000493:pharmacokinetics*; D017837:Bothrops; D002460:Cell Line; D006801:Humans; D008297:Male; D051379:Mice; D010455:Peptides / Q000737:chemistry / Q000493:pharmacokinetics*; D011392:Proline; D030162:Reptilian Proteins / Q000737:chemistry / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D000959:Antihypertensive Agents; D010455:Peptides; D030162:Reptilian Proteins; D011392:Proline