The vasodilatory properties of recombinant maxadilan.
Jackson, Terence, Ethan Lerner, Robert M. Weisbrod, Masahiro Tajima,
Joseph Loscalzo, and John F. Keaney, Jr.
Evans Memorial Department of Medicine and Whitaker Cardiovascular
Institute, Boston Unversity School of Medicine, Boston, MA, 02118;
_MGH Cutaneous Biology Research Center, Harvard Medical School,
Boston, MA, 02129, and Shiseido Research Center, Yokohama, Kanagawa,
236, Japan
APStracts 3:0033H, 1996.
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 an EC50 of 2.7 +/- 1.5 nM, 2.1 +/- 0.5 nM, 2.6 +/- 0.4
nM, and 1.9 +/- 0.5 nM, respectively. Maxadilan proved at least 7
-fold more potent than nitroglycerin in eacharterial bed (EC50 = 25
+/- 12 nM, 32 +/- 9 nM, 37 +/- 10 nM, 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 cAMP-dependent as it was potentiated by
the phosphodiesterase inhibitors IBMX and theophylline, and inhibited
by the protein kinase A inhibitor H-89. Consistent with this
observation, incubation of thoracic aorta with maxadilan (0.1 [mu]M)
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.
Received 9 August 1995; accepted in final form 12 January 1996.
APS Manuscript Number H747-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 25 January 96