Evidence that cultured airway smooth muscle cells contain bradykinin B2 and B3 receptors.
We examined bradykinin-induced 45Ca2+ efflux and prostaglandin synthesis in guinea pig tracheal smooth muscle cells maintained in tissue culture. We also studied the effects of a B1 receptor agonist and antagonist, a B2 receptor antagonist, and the cyclooxygenase inhibitor indomethacin. In cultured smooth muscle cells, bradykinin (0.1 nM to 10 microM) stimulated efflux of 45Ca2+ and induced the synthesis of prostaglandin E2 and the prostacyclin metabolite 6-keto-prostaglandin F1 alpha. DesArg9-bradykinin, a B1 receptor agonist, had no effect on 45Ca2+ efflux or prostaglandin synthesis, and no responses to bradykinin were unaffected by the B1 receptor antagonist desArg9-[Leu8]-bradykinin. Indomethacin (1 microM) abolished bradykinin-induced prostaglandin synthesis but was without effect on 45Ca2+ efflux. NPC 567 (DArg[Hyp3,DPhe7]-bradykinin), a B2 receptor antagonist, had no effect on bradykinin-induced 45Ca2+ efflux, but abolished prostaglandin synthesis. Unlike in membranes prepared freshly from guinea pig tracheal smooth muscle, the B2 receptor antagonist inhibited completely (Ki, 12 nM) binding of [3H]-bradykinin to membranes prepared from cultured tracheal smooth cells. These data suggest that tracheal smooth muscle cells, maintained in culture, express B2 receptors that mediate bradykinin-induced prostaglandin synthesis. The observation that bradykinin-induced efflux of calcium ions was unaffected by B1 or B2 antagonists provides further evidence that airway smooth muscle may contain a novel B3 receptor.
Farmer
S G
SG
Nova Pharmaceutical Corporation, Baltimore, Maryland.
Ensor
J E
JE
Burch
R M
RM
D000818:Animals; D001920:Bradykinin / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D006168:Guinea Pigs; D008297:Male; D009130:Muscle, Smooth / Q000378:metabolism*; D011453:Prostaglandins / Q000096:biosynthesis*; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter / Q000032:analysis* / Q000145:classification; D014132:Trachea / Q000378:metabolism*; D014316:Tritium
D011453:Prostaglandins; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter; D014316:Tritium; D001920:Bradykinin; D002118:Calcium