Uddman R, Goadsby P J, Jansen-Olesen I, Edvinsson L
Department of Otorhinolaryngology, General Hospital, Malmö, Sweden.
J Cereb Blood Flow Metab. 1999 Jan;19(1):61-7. doi: 10.1097/00004647-199901000-00007.
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.
希洛肽素I和II以及希洛德明是未酰胺化的、血管活性肠肽（VIP）样肽，从钝尾毒蜥和墨西哥毒蜥的唾液腺毒液中分离得到。希洛肽素I有38个氨基酸残基，与希洛肽素II的不同之处在于其C末端有一个额外的丝氨酸残基。在猫脑动脉的外膜和外膜-中膜交界处存在许多含有希洛肽素样免疫反应性（LI）的神经纤维以及少数含有希洛德明-LI的纤维。在蝶腭神经节中，可见许多含有希洛肽素-LI的神经细胞体。双重免疫染色显示，含有希洛肽素-LI的神经细胞体与含有VIP的细胞体共存。放射免疫分析表明， Willis环脑血管提取物中希洛肽素-LI水平很高（27.4 pg/mg [重量/重量]）。希洛肽素I和II以及希洛德明（10⁻¹⁰至10⁻⁶ mol/L）可使猫大脑中动脉产生浓度依赖性舒张作用，舒张程度达U46619诱导的预收缩的50%至80%。最大效应和效力与VIP相似。这些肽均未引起内皮依赖性舒张。向α-氯醛糖麻醉的猫脑内微量注射希洛肽素和希洛德明可使脑血流量产生适度的浓度依赖性增加。注射5微克希洛德明后观察到最大增加量（21±5%），而希洛肽素I为16±7%，希洛肽素II为19±5%。结果表明，希洛肽素/希洛德明样肽与VIP在起源于蝶腭神经节的血管周围神经纤维中共定位。它们似乎具有强大的血管舒张作用。
