dinoprost and heliodermin

The present study was designed to study the localization and effects of some VIP-related peptides on the cerebral circulation in cats. A rich supply of nerve fibres containing vasoactive intestinal peptide- (VIP) was seen. Nerve fibres containing pituitary adenylate cyclase activating peptide and helospectin-like immunoreactivity (-IR) were moderate in numbers whereas only a sparse supply of fibres containing helodermin-IR was seen. Double immunostaining revealed that the majority of PACAP- and helospectin-IR nerve fibres contained VIP. Using a sensitive in vitro system prostaglandin F2 alpha-precontracted circular segments of the cat middle cerebral artery relaxed upon administration of VIP, PACAP, helospectin I, helospectin II and helodermin. These effects were non-endothelium dependent with pD2-values varying between 7.6 and 8.1. The maximum relaxation varied between 47% and 79% of precontraction. Local cerebral blood flow was studied in anaesthetised cats. Cortical injection of PACAP-38, helospectin or helodermin, 5 micrograms in a volume of 1 microliter, revealed moderate and consistent increases in flow. The increase in cerebral blood flow was rapid and concentration-dependent with maximum increases of 18 +/- 6% for PACAP, 21 +/- 5% for helodermin, 16 +/- 7% for helospectin I and 19 +/- 5% for helospectin II. The vehicle caused no significant response (2 +/- 4%).

Topics: Animals; Cats; Cerebral Arteries; Cerebrovascular Circulation; Dinoprost; Endothelium, Vascular; Immunohistochemistry; Intercellular Signaling Peptides and Proteins; Laser-Doppler Flowmetry; Neuropeptides; Peptides; Pituitary Adenylate Cyclase-Activating Polypeptide; Vasoactive Intestinal Peptide

1. Helodermin, helospectin I and helospectin II, peptides recently isolated from the salivary gland venom of Heloderma suspectum, were compared to vasoactive intestinal peptide (VIP) with respect to effects on systemic blood pressure and on isolated femoral arteries in the rat. 2. They all reduced blood pressure in a dose-dependent manner; helodermin was less effective than VIP. However, at doses higher than 1 nmol kg-1 all four peptides reduced blood pressure to about the same extent. 3. The half-life of the hypotensive effect of VIP was longer than that of helodermin and the helospectins. 4. VIP and helodermin were equally potent in relaxing femoral arteries precontracted with phenylephrine or prostaglandin F2 alpha. 5. Helospectin I and II relaxed phenylephrine-contracted vessels to the same extent as VIP but with a lower potency. 6. Addition of VIP 1 microM to preparations exposed to helodermin 1 microM or to either of the helospectins did not produce a further relaxation. 7. The findings indicate that VIP, helodermin and helospectin I and II have a similar profile of action and therefore may act on a common receptor.

Topics: Amino Acid Sequence; Animals; Blood Pressure; Dinoprost; Female; Half-Life; Hemodynamics; In Vitro Techniques; Intercellular Signaling Peptides and Proteins; Male; Molecular Sequence Data; Peptides; Phenylephrine; Rats; Rats, Inbred Strains; Vasoactive Intestinal Peptide