Role of intracellular alkalinization in the inhibition of
acetylcholine-induced relaxation by fmlp in rat aorta.
Ando, Katsuyuki, and Toshiro Fujita.
Fourth Department of Internal Medicine, University of Tokyo School
of Medicine, Tokyo 112, Japan
APStracts 3:0275H, 1996.
N-formyl-methionyl-leucyl-phenylalanine, a chemotactic tripeptide, is
known to cause intracellular alkalinization. Moreover, there is a
specific receptor for this formyl peptide in vascular endothelial
cells but not in vascular smooth muscle cells. Since we have already
reported that intracellular alkalinization inhibits acetylcholine
-induced relaxation, we examined whether the formyl peptide alters the
vasodilation of endothelial cells through intracellular
alkalinization. The formyl peptide reduced acetylcholine-induced
relaxation in aortic rings from Sprague-Dawley rats but did not
affect nitroglycerin-induced relaxation. N-t-butoxycarbonyl
-phenylalanyl-D-leucyl-phenylalanyl-D-leucyl-phenylalanine, a specific
formyl receptor antagonist, reversed the impairment of acetylcholine
-induced relaxation, as did the protein kinase C inhibitors,
sphingosine and 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7).
The sodium-proton antiport inhibitor, amiloride, and the proton
ionophore, nigericin, normalized the attenuated acetylcholine-induced
relaxation. The formyl peptide-induced impairment was normalized by
the phospholipase A2 inhibitor, quinacrine, the cyclooxygenase
inhibitor, indomethacin, and the antagonists of the prostaglandin H2
and/or thromboxane A2 receptor, ONO3708 and S1452. Superoxide
dismutase inhibited the effect of the formyl peptide. In conclusion,
N-formyl-methionyl-leucyl-phenylalanine attenuated acetylcholine
-induced relaxation, possibly through intracellular alkalinization.
Increased production of vasoconstrictor prostaglandin(s) and
superoxide may contribute to the inhibitory effect of the formyl
peptide-induced alkalinization on acetylcholine-induced relaxation.
Received 11 December 1995; accepted in final form 10 June 1996.
APS Manuscript Number H1152-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 25 July 1996