IN-VITRO AND IN-VIVO EVIDENCE FOR A TACHYKININ NK1 RECEPTOR ANTAGONIST EFFECT OF VAPREOTIDE, AN ANALGESIC CYCLIC ANALOG OF SOMATOSTATIN

Vapreotide, a long-acting somatostatin analog, possesses an analgesic effect. The purpose of this work was to determine a tachykinergic involvement. Vapreotide reduced substance P-induced biting and scratching in mice. This inhibitory effect of substance P action was confirmed by experiments performed on the bronchial apparatus of guinea-pigs known to possess tachykinin NK1 and NK2 receptors. (i) Vapreotide reduced the substance P-induced plasmatic exudation. (ii) It inhibited selectively the tachykinin-dependent second contractile phase induced by electrical field stimulation of isolated bronchi. (iii) It shifted to the right the concentration-effect curve of substance P-induced contraction of isolated main bronchi. The peptide displaced [H-3]substance P (IC50 = 3.3 +/- 1.8 X 10(-7) M) from guinea-pig bronchial tachykinin NK, sites. The displacement of [I-125]neurokinin A, a specific tachykinin NK2 receptor ligand, needed higher concentrations (IC50 = 4.5 +/- 0.6 X 10(-6) M). It is concluded that vapreotide possesses an antagonist activity on guinea-pig tachykinin NK1 receptors; the involvement in its analgesic action is discussed.