RESUMO
This study was performed on two novel VIP analogues; namely, [N1e17, A1a24, A1a25, Va126]-VIP-[1-27]-NH2 [analogue 1] and [Ser [SO3H]3, Nle17-VIP [analogue 2], which were obtained by undergoing certain changes in the amino acid sequence of the VIP molecule in a trial to reach a novel more stable, but still active form of VIP. Relative potency as well as duration of action of the two analogues was tested versus that of native VIP on isolated guinea pig tracheal strips placed in organ baths. Changes in smooth muscle tension were measured by isometric force transducers and recorded continuously. Analogue 1 was significantly more potent and had a significantly longer duration of action than natural VIP as a tracheal relaxant at the lower concentration range of 5 x 10-9 M to 5 x 10-8 M and its maximal relaxing effect was 72% of that of native VIP. Analogue 2 was significantly much less potent than natural VIP at all concentrations tested with maximal potency of only 11% of that of native VIP and showed shorter duration of action. However, it significantly reduced VIP-induced tracheal relaxation. The encouraging results with analogue 1 suggest its clinical trial in therapy of bronchial asthma. As VIP antagonists may potently inhibit the basal growth of cancer cells in vitro and certain tumors in vivo, especially lung carcinoma, analogue 2 may serve as a useful candidate in this respect. The interesting findings with the two analogues suggest further investigation to enhance their potency, whether agonistic [for analogue 1] or antagonistic [for analogue 2], at VIP receptors by additional changes in their molecules to improve the chance of possible clinical applications