Identification and transmembrane signaling of leukotriene D sub 4 receptors in human mesangial cells
- Case Western Reserve Univ., Cleveland, OH (USA) University Hospitals of Cleveland, OH (USA)
Although peptidoleukotriene (LTC{sub 4}, LTD{sub 4}) receptors have been characterized by radioligand binding studies, pathways of transmembrane signaling by activated leukotriene receptors remain obscure. The authors employed ({sup 3}H)LTD{sub 4} binding studies and fluorescent measurements of intracellular Ca{sup 2+} concentration ((Ca{sup 2+})) and pH to identify LTD{sub 4} receptors and mechanisms of transmembrane signaling in cultured human mesangial cells. Mesangial cells expressed a single class of saturable, specific binding sites for ({sup 3}H)LTD{sub 4}. Kinetic, competition, and saturation analyses gave an average K{sub D} of {approximately}12.0 nM with a B{sub max} of 987 fmol/mg protein. LTC{sub 4} competed with high affinity for ({sup 3}H)LTD{sub 4} binding sites, as did LTB{sub 4} but with much lower affinity. ({sup 3}H)LTD{sub 4} binding was blocked by a specific LTD{sub 4} receptor antagonist, SKF 102922. LTD{sub 4} and LTC{sub 4} also evoked a rapid, transient increase in intracellular (Ca{sup 2+}), followed by a second, sustained increase. They also report evidence that LTD{sub 4} affects intracellular pH and activates Na{sup +}-H{sup +} exchange. Specifically, LTD{sub 4} induced an initial acidification within 1-2 min, followed by net alkalinization at 5 min. Alkalinization was due to activation of an amiloride-inhibitable Na{sup +}-H{sup +} exchanger. They conclude that ({sup 3}H)LTD{sub 4} binding sites on human mesangial cells are coupled to a Ca{sup 2+}-signaling system and Na{sup +}-H{sup +} exchange.
- OSTI ID:
- 6289530
- Journal Information:
- American Journal of Physiology; (USA), Journal Name: American Journal of Physiology; (USA) Vol. 255:6; ISSN 0002-9513; ISSN AJPHA
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
ALKALINE EARTH METAL COMPOUNDS
BIOCHEMICAL REACTION KINETICS
BODY
CALCIUM COMPOUNDS
CELL CONSTITUENTS
CELL MEMBRANES
CHEMICAL ACTIVATION
DOSE-RESPONSE RELATIONSHIPS
HYDROGEN COMPOUNDS
KIDNEYS
KINETICS
LIGANDS
MEMBRANE PROTEINS
MEMBRANES
ORGANIC COMPOUNDS
ORGANS
PEPTIDES
PH VALUE
PROTEINS
REACTION KINETICS
RECEPTORS
TRITIUM COMPOUNDS