Bradykinin (Bk) increases cytosolic calcium in cultured rat myenteric neurons via Bk-2 type receptors coupled to mobilization of extracellular and intracellular sources of calcium: evidence that calcium influx is prostaglandin dependent.
We examined the effect of bradykinin (Bk) on cytosolic calcium ([Ca++]i) in cultured rat ileal myenteric neurons. The receptor subtype(s) and calcium pool(s), e.g., extracellular and/or intracellular calcium that mediate Bk's effect on [Ca++]i in myenteric neurons, have not been reported. Superfusion with Bk (10 nM) increased [Ca++]i by 96 +/- 10 nM over basal levels in approximately 80% of the neurons tested that were not affected by a Bk-1 receptor antagonist but were inhibited 72% by a Bk-2 receptor antagonist. The Bk-generated increase in [Ca++]i was reduced by 45% and 52% of control response in calcium-free buffer and indomethacin, respectively, supporting involvement of extracellular and intracellular pools of calcium and mediation, in part, by a prostaglandin-dependent pathway. Bk increased [Ca2++]i by 54 +/- 6 nM in calcium-free buffer that was indomethacin insensitive, suggesting that Bk stimulation of extracellular calcium influx was mediated by a prostaglandin-dependent pathway. Bk (1 microM) increased tissue prostaglandin E2 (PGE2) production by 62% over basal levels in isolated rat ileal myenteric ganglia. Finally, superfusion with PGE2 (10 microM) increased [Ca++]i by 105 +/- 16 nM over basal levels that were blocked in calcium-free buffer. In summary, our studies suggest that cultured rat ileal myenteric neurons express the Bk-2 receptor subtype that is coupled to mobilization of extracellular and intracellular pools of calcium. Bk stimulates influx of extracellular calcium via a prostaglandin-dependent pathway.
Gelperin
D
D
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor.
Mann
D
D
del Valle
J
J
Wiley
J W
JW
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D015232:Dinoprostone / Q000096:biosynthesis; D007213:Indomethacin / Q000494:pharmacology; D009197:Myenteric Plexus / Q000378:metabolism*; D011453:Prostaglandins / Q000502:physiology*; D051381:Rats; D018002:Receptors, Bradykinin / Q000187:drug effects / Q000502:physiology*
D011453:Prostaglandins; D018002:Receptors, Bradykinin; D015232:Dinoprostone; D001920:Bradykinin; D002118:Calcium; D007213:Indomethacin