Salivary gland homogenates of Lutzomyia longipalpis and its vasodilatory peptide maxadilan cause plasma leakage via PAC1 receptor activation.
OBJECTIVE
Experiments were designed to determine if salivary gland homogenates (SGH) of the sand fly Lutzomyia longipalpis, the vasodilatory peptides maxadilan and pituitary adenylate cyclase-activating peptide (PACAP-38) may cause plasma leakage and to what extent these effects could be due to PAC1 receptor stimulation.


METHODS
Using FITC-dextran as a plasma marker, intravital microscopy of the hamster cheek pouch (HCP) and a digital camera were used to assess arteriolar diameter and fluorescence of a selected area (5 mm(2)) representative of the HCP microcirculation.


RESULTS
Cheek pouches prepared for intravital microscopy and exposed to topical application of SGH, maxadilan or PACAP-38 developed maximal dilation of arterioles in the range of 20-60 mum within 10 min, and this effect lasted for 30-90 min. The increase in fluorescence intensity induced by each of these compounds was due to plasma leakage from postcapillary venules. The mutant peptide of maxadilan (M-65), a PAC1 receptor antagonist, inhibited both dilation and plasma leakage induced by SGH or maxadilan. Plasma leakage induced by SGH was modestly inhibited by the bradykinin B(2) receptor antagonist HOE-140, but not by the antihistamine mepyramine or the nitric oxide synthase inhibitor L-NA.


CONCLUSIONS
SGH of L. longipalpis and its vasodilatory peptide maxadilan caused long-lasting arteriolar dilation and plasma leakage in the cheek pouch via PAC1 receptor activation.
Svensjö
Erik
E
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil. erik.svensjo@gmail.com
Saraiva
Elvira M
EM
Bozza
Marcelo T
MT
Oliveira
Sandra M P
SM
Lerner
Ethan A
EA
Scharfstein
Julio
J
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000378:metabolism; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D006224:Cricetinae; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D019476:Insect Proteins / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D008856:Microscopy, Fluorescence; D019335:Nitroarginine / Q000494:pharmacology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000378:metabolism; D010949:Plasma / Q000378:metabolism; D011576:Psychodidae / Q000378:metabolism*; D011738:Pyrilamine / Q000494:pharmacology; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I / Q000378:metabolism*; D012469:Salivary Glands / Q000378:metabolism*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000378:metabolism* / Q000494:pharmacology; D014699:Venules / Q000187:drug effects / Q000378:metabolism
D000319:Adrenergic beta-Antagonists; D004791:Enzyme Inhibitors; D006634:Histamine H1 Antagonists; D019476:Insect Proteins; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D014665:Vasodilator Agents; C069147:maxadilan protein, insect; D019335:Nitroarginine; C065679:icatibant; D011738:Pyrilamine; D001920:Bradykinin