| 1. |
- Sergejeva, Svetlana, 1972, et al.
(författare)
-
A synthetic VIP peptide analogue inhibits neutrophil recruitment in rat airways in vivo
- 2004
-
Ingår i: Regulatory peptides. - : Elsevier BV. - 0167-0115. ; 117:2, s. 149-54
-
Tidskriftsartikel (refereegranskat)abstract
- Currently, there is no effective pharmacotherapy against exaggerated mobilisation of neutrophils in human airway diseases such as chronic obstructive pulmonary disease and asthma. We evaluated the effect of two synthetic vasoactive intestinal peptide (VIP)-like analogues on cytokine-induced neutrophil recruitment in airways in vivo. Recombinant interleukin (IL)-1 beta was administered intratracheally (i.t.) to intubated, spontaneously breathing Sprague-Dawley rats. The rats were pretreated either with a VIP synthetic peptide analogue, a pituitary adenylate cyclase-activating peptide (PACAP)-1-27 synthetic analogue, the beta(2)-adrenoceptor agonist salbutamol or vehicle, systemically or locally. Differential cell counts were performed on bronchoalveolar lavage fluid (BALf) cytospins. Effects on mean arterial blood pressure (MAP) were monitored in separate experiments. Systemic administration of the VIP analogue, the PACAP analogue and salbutamol attenuated the cytokine-induced increase in BALf neutrophil number. Local administration of the VIP analogue and salbutamol, but not the PACAP analogue, also decreased the neutrophil number in BALf. Local administration of the VIP analogue and salbutamol caused a transient decrease in MAP. Systemic or local administration of a synthetic VIP peptide analogue inhibits cytokine-induced neutrophil recruitment in airways in vivo. This action is exerted without severe, sustained cardiovascular side effects, and deserves to be further evaluated in obstructive pulmonary diseases in human.
|
|
| 2. |
|
|
| 3. |
- Yoshihara, S., et al.
(författare)
-
Long-lasting smooth-muscle relaxation by a novel PACAP analogue in human bronchi
- 2004
-
Ingår i: Regul Pept. ; 123:1-3
-
Tidskriftsartikel (refereegranskat)abstract
- We compared the relaxant effect of original pituitary adenylate cyclase-activating peptide (PACAP)1-27 with that of a newly developed, synthetic PACAP1-27 analogue, [Arg(15,20,21) Leu(17)]-PACAP-Gly-Lys-Arg-NH(2), in human bronchi in vitro (n=4-5 in each group). Using precontraction by carbachol (0.1 muM), cumulative administration of PACAP1-27 and salbutamol caused concentration-dependent smooth muscle relaxation with similar potencies and maximum relaxant effects. Non-cumulative administration of the PACAP1-27 analogue and the original PACAP1-27 caused concentration-dependent relaxation with a similar maximum relaxant effect and potency as well. However, the onset and offset of action was markedly slower for the PACAP1-27 analogue than for the original PACAP1-27 (>90% versus <10% of peak relaxation remaining 5 h after administration). Peptidase inhibition by captopril (10 muM) and phosphoramidon (1 muM) significantly increased the maximum relaxant effect and duration of action of PACAP1-27 but not of the PACAP1-27 analogue, during the 3 h of observation in the human bronchi. We conclude that [Arg(15,20,21) Leu(17)]-PACAP-Gly-Lys-Arg-NH(2) produces significant concentration-dependent and sustained bronchial smooth muscle relaxation in vitro. The sustained relaxant effect is due, at least in part, to the synthetic PACAP1-27 analogue being less susceptible to cleavage by peptidases than the original peptide PACAP1-27.
|
|
