caa a22 4500 469078138 CHVBK 20180323132941.0 cr unu---uuuuu 170328e19920901xx s 000 0 eng 10.1007/BF00173543 doi (NATIONALLICENCE)springer-10.1007/BF00173543 Identification of a B2-bradykinin receptor linked to phospholipase C and inhibition of dopamine stimulated cyclic AMP accumulation in the human astrocytoma cell line D384 [Elektronische Daten] [Anthony Balmforth, Fiona Parkinson, Nedret Altiok, Bertil Fredholm] Summary: We have examined the activation of a phospholipase C signal transduction pathway by a B2-bradykinin receptor in the human astrocytoma cell line D384 and how this influences D1-dopamine receptor stimulated cyclic AMP accumulation. Addition of bradykinin to D384 cells resulted in a concentration-dependent (10−11 − 10−6 M) increase in the accumulation of [3H]inositol phosphates and a similar concentration-dependent transient increase in specific [3H]β-phorbol-12,13-dibutyrate binding which is indicative of translocation of protein kinase C from the cytosol to the membrane. Changes in intracellular Ca2+ of single cells, measured using the fluorescent indicator dye fura-2, indicated that bradykinin produced a rapid, but transient, increase in intracellular calcium. The Ca2+ response was largely independent of extracellular Ca2+ supporting the idea that receptor activation leads to mobilization of Ca2+ from intracellular stores. However, extracellular Ca2+ was required for a response to a rechallenge with bradykinin. The bradykinin B2-receptor agonist kallidin increased cytosolic Ca 2+ in a similar manner to bradykinin. The Ca2+ response to bradykinin could be partially reduced in the presence of the B2-receptor antagonist [d-Arg10-Hyp,d-Phe7,β-(2-Thienyl)-Ala5,8]-bradykinin, whereas the B1-receptor agonists (Des-Arg9]-bradykinin and [Des-Arg10]-kallidin were ineffective. Bradykinin was also found to attenuate dopamine stimulated cyclic AMP accumulation in D384 cells, at similar concentrations previously observed to stimulate the phospholipase C signal transduction pathway, in the presence of the phosphodiesterase inhibitor, rolipram. In contrast, no attenuation was observed in the presence of the phosphodiesterase inhibitor 1-isobutyl 3-methylxanthine, although the level of dopamine stimulated cyclic AMP observed was lower than in the presence of rolipram. Furthermore, the effect of bradykinin could be mimicked by a calcium ionophore, but not a phorbol ester. These data suggest that D384 cells express a B2 bradykinin receptor coupled to polyphosphoinositide-specific phospholipase C. Activation of this receptor results in elevated levels of cytosolic Ca2+ and to a reduction of D1-dopamine receptor stimulated cyclic AMP accumulation. Springer-Verlag, 1992 B2-Bradykinin receptor nationallicence Intracellular calcium nationallicence Phorbol ester binding nationallicence Cyclic AMP nationallicence D1-dopamine receptor nationallicence Phosphodiesterase nationallicence Balmforth Anthony Department of Cardiovascular Studies, University of Leeds, LS2 9JT, Leeds, England aut Parkinson Fiona Department of Pharmacology, Karolinska Institutet, Stockholm, Sweden aut Altiok Nedret Department of Pharmacology, Karolinska Institutet, Stockholm, Sweden aut Fredholm Bertil Department of Pharmacology, Karolinska Institutet, Stockholm, Sweden aut Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 346/3(1992-09-01), 303-310 0028-1298 346:3<303 1992 346 210 https://doi.org/10.1007/BF00173543 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00173543 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Balmforth Anthony Department of Cardiovascular Studies, University of Leeds, LS2 9JT, Leeds, England aut NATIONALLICENCE 700 1- Parkinson Fiona Department of Pharmacology, Karolinska Institutet, Stockholm, Sweden aut NATIONALLICENCE 700 1- Altiok Nedret Department of Pharmacology, Karolinska Institutet, Stockholm, Sweden aut NATIONALLICENCE 700 1- Fredholm Bertil Department of Pharmacology, Karolinska Institutet, Stockholm, Sweden aut NATIONALLICENCE 773 0- Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 346/3(1992-09-01), 303-310 0028-1298 346:3<303 1992 346 210 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer