Identification of a B2 bradykinin receptor expressed by PC12 pheochromocytoma cells.

AUTOR(ES)

Nardone, J

RESUMO

We have used rat PC12 pheochromocytoma cells, a clonal cell line closely related to sympathetic neurons, to investigate reports that the bradykinin receptor expressed in the peripheral nervous system is distinct from the well-characterized B2 bradykinin receptor of smooth muscle. Although there have been reports that [Thi5,8,D-Phe7]bradykinin [where Thi is beta-(2-thienyl)alanine] is a full agonist at some sites in the peripheral nervous system, we find that in PC12 cells [Thi5,8,D-Phe7]bradykinin behaves as a competitive antagonist of bradykinin-stimulated phosphatidylinositol turnover. In particular, sufficient concentrations of [Thi5,8,D-Phe7]bradykinin completely block the increase in inositol bisphosphate and trisphosphate in response to 100 nM bradykinin; [Thi5,8,D-Phe7]bradykinin alone, at up to 10 microM, does not appreciably increase inositol bisphosphate and trisphosphate. In contrast to the absence of evidence for a distinctive neuronal receptor, we have found convincing evidence that the bradykinin receptor previously identified in smooth muscle is present in PC12 cells. Using the polymerase chain reaction, we have isolated a full-length cDNA encoding a bradykinin receptor that is expressed in PC12 cells and verified that its nucleotide sequence is identical except at a single position to that of the rat uterine B2 bradykinin receptor. When expressed in COS cells this uterine bradykinin receptor exhibits the same high affinity for [3H]bradykinin (Kd 4.4 nM), the same relative affinities for a series of kinin antagonists, and the same efficient coupling to phosphatidylinositol turnover (EC50 2.5 nM) as the receptor in PC12 cells. We interpret our data, and the findings of a number of pharmacological studies, as strengthening the view that the B2 receptor expressed in PC12 cells and in certain cells of the peripheral nervous system is identical to the receptor in rat uterine smooth muscle.

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