Helospectin-like peptides: Immunochemical localization and effects on isolated cerebral arteries and on local cerebral blood flow in the cat

Helospectin I and II and helodermin are nonamidated, vasoactive intestinal peptide (VIP)-like peptides, isolated from the salivary gland venom of the lizards Heloderma suspectum and Heloderma horridum. Helospectin I has 38 am ino acid residues and differs from helospectin II in that it has an additio nal serine residue at the C-terminus. Numerous nerve fibers containing helo spectin-like immunoreactivity (LI) and a few fibers containing helodermin-L I were present in the adventitia and at the adventitia-media border of cat cerebral arteries. In the sphenopalatine ganglion, numerous nerve cell bodi es containing helospectin-LI were seen. Double immunostaining revealed that helospectin-LI nerve cell bodies coexisted with VIP-containing cell bodies . Radioimmunoassay showed high levels of helospectin-LI in extracts of cere bral vessels from the circle of Willis (27.4 pg/mg [wt/wt]). Helospectin I and II and helodermin (10(-10) to 10(-6) mol/L) produced concentration-depe ndent relaxations of feline middle cerebral arteries amounting to 50% to 80 % of precontraction induced by U46619. The maximum effects and the potency were similar to that of VIP. Neither of these peptides elicited endothelium -dependent relaxations. Intracerebral microinjection of helospectin and hel odermin produced a moderate concentration-dependent increase of the cerebra l blood flow of a-chloralose anesthetized cats. The maximum increase (21 +/ - 5%) was observed after the injection of 5 mu g helodermin, whereas 16 +/- 7% was seen with helospectin I and 19 +/- 5% with helospectin IT. The resu lts suggest that helospectin/helodermin-like peptides co-localize with VIP in perivascular nerve fibers originating in the sphenopalatine ganglion. Th ey seem to have strong and potent vasodilator effects.