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

Abstract

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 amino acid residues and differs from helospectin II in that it has an additional serine residue at the C-terminus. Numerous nerve fibers containing helospectin-like immunoreactivity (LI) and a few fibers containing helodermin-LI were present in the adventitia and at the adventitia-media border of cat cerebral arteries. In the sphenopalatine ganglion, numerous nerve cell bodies 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 cerebral 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-dependent 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 helodermin produced a moderate concentration-dependent increase of the cerebral blood flow of alpha-chloralose anesthetized cats. The maximum increase (21 +/- 5%) was observed after the injection of 5 microg helodermin, whereas 16 +/- 7% was seen with helospectin I and 19 + 5% with helospectin II. The results suggest that helospectin/helodermin-like peptides co-localize with VIP in perivascular nerve fibers originating in the sphenopalatine ganglion. They seem to have strong and potent vasodilator effects.