title: Salivary gland homogenates of Lutzomyia longipalpis and its vasodilatory peptide maxadilan cause plasma leakage via PAC1 receptor activation.
abstract: 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.
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil. erik.svensjo@gmail.com
authors.forename: Erik
authors.initials: E
authors.lastname: Svensjö
authors.forename: Elvira M
authors.initials: EM
authors.lastname: Saraiva
authors.forename: Marcelo T
authors.initials: MT
authors.lastname: Bozza
authors.forename: Sandra M P
authors.initials: SM
authors.lastname: Oliveira
authors.forename: Ethan A
authors.initials: EA
authors.lastname: Lerner
authors.forename: Julio
authors.initials: J
authors.lastname: Scharfstein
mesh_terms: 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
chemical_list: 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