Vasodilatory properties of recombinant maxadilan.
Maxadilan is a peptide from the salivary gland of the sand fly Lutzomyia longipalpis, a vector for leishmaniasis. Cutaneous injection of femtomolar quantities of maxadilan produces long-lasting erythema, making it the most potent vasodilator known. Isolated rabbit thoracic and abdominal aorta, carotid artery, and iliac artery demonstrated dose-dependent arterial relaxation in response to maxadilan with a mean effective concentration (EC50) of 2.7 +/- 1.5, 2.1 +/- 0.5, 2.6 +/- 0.4, and 1.9 +/- 0.5 nM, respectively. Maxadilan proved to be at least sevenfold more potent than nitroglycerin in each arterial bed (EC50 = 25 +/- 12, 32 +/- 9, 37 +/- 10, and 22 +/- 13 nM, respectively; P < 0.05 for each vs. maxadilan). Arterial relaxation to maxadilan was independent of endothelium and was equipotent in the thoracic and abdominal aorta, carotid artery, and iliac artery. Arterial relaxation to maxadilan was not inhibited by K(+)-channel antagonists, methylene blue, quinacrine, or ouabain. Maxadilan-mediated arterial relaxation was found to be adenosine 3',5'-cyclic monophosphate (cAMP) dependent, as it was potentiated by the phosphodiesterase inhibitors 3-isobutyl-1-methylxanthine and theophylline, and it was inhibited by the protein kinase A inhibitor H-89. Consistent with this observation, incubation of thoracic aorta with maxadilan (0.1 microM) produced a time-dependent increase in arterial cAMP content coincident with arterial relaxation. Using rabbit aortic smooth muscle cells, we also observed a time-dependent reduction in intracellular calcium in response to maxadilan. Thus these data indicate that maxadilan, a peptide from the sand fly salivary gland, is a potent vasodilator that reduces intracellular calcium through a cAMP-dependent mechanism.
Jackson
T S
TS
Evans Memorial Department of Medicine, Boston University School of Medicine 02118, USA.
Lerner
E
E
Weisbrod
R M
RM
Tajima
M
M
Loscalzo
J
J
Keaney
J F
JF
D000818:Animals; D001158:Arteries / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D007301:Insect Hormones / Q000494:pharmacology*; D019476:Insect Proteins; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D011817:Rabbits; D011994:Recombinant Proteins; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology*
D007301:Insect Hormones; D019476:Insect Proteins; D011994:Recombinant Proteins; D014665:Vasodilator Agents; C069147:maxadilan protein, insect