The effect of vasoactive intestinal peptide (VIP) was studied on the contractile response of guineaâpig lung parenchymal strips (GPP) induced by bronchoconstrictor agonists, such as leukotriene D4 (LTD4), histamine and acetylcholine (ACh). This effect of VIP was compared with helodermin, a peptide that is structurally related to VIP, and galanin, another neuropeptide that is thought to coâexist with VIP.
VIP (10 nm) induced a potent and reversible inhibition of the contractions of GPP induced by LTD4 (1â30 pmol) but did not affect those due to ACh (1â100 nmol) or histamine (1â30 nmol). A ten fold higher concentration of VIP (100 nm) did not further inhibit LTD4âinduced responses or reduce those induced by histamine or ACh.
Helodermin (10 nm) had a similar inhibitory effect on contractions of GPP induced by LTD4 (3â30 pmol) but did not affect contractions induced by histamine (1â10 nmol).
Indomethacin (2.8 ÎŒm) and salbutamol (10 nm) significantly reduced responses elicited by LTD4 and histamine but not those due to ACh. A ten fold higher concentration of salbutamol (100 nm) further inhibited the contractions due to LTD4 and histamine and at this concentration responses induced by ACh were inhibited.
VIP (10 nm) and helodermin (10 nm) significantly reduced the LTD4âinduced release of thromboxane A2 (TXA2), measured as TxB2 by radioimmunoassay, from GPP. The smaller release of TxA2 induced by histamine was not significantly reduced in the presence of VIP.
In comparative studies, galanin (10â100 nm) did not affect contractions of GPP induced by either LTD4, histamine or ACh. In contrast to VIP and helodermin, both at 0.1â3 nmol, which induced doseârelated relaxations of guineaâpig trachea, galanin was inactive on this preparation in doses of up to 3 nmol.
In conclusion, our results show that contractions of GPP induced by LTD4 are more sensitive to inhibition by VIP and helodermin than are contractions due to histamine or ACh. This inhibition appears to be associated with the different contribution of released TxA2 to contractions evoked by the agonists. VIP and helodermin inhibit the cycloâoxygenaseâdependent component of the LTD4âinduced response, as in the case of indomethacin.