DOI: 10.1111/j.1476-5381.1993.tb13984.x. Homologous and heterologous desensitization of histamine H<sub>1</sub>‐and ATP‐receptors in the smooth muscle cell line, DDT<sub>1</sub>MF‐2: the role of protein kinase C

Homologous and heterologous desensitization of histamine H1‐and ATP‐receptors in the smooth muscle cell line, DDT1MF‐2: the role of protein kinase C

10.1111/j.1476-5381.1993.tb13984.x

Crossref journal-article

Wiley

British Journal of Pharmacology (311)

Abstract

The possible role of protein kinase C (PKC) in homologous and heterologous desensitization of histamine H1‐ and ATP‐receptors has been studied in monolayers of cultured vas deferens smooth muscle cells (DDT1MF‐2). Cells were loaded with the calcium‐sensitive fluorescent dye fura‐2 and increases in intracellular free Ca2+concentration ([Ca2+]i) monitored in response to histamine H1‐ or ATP‐receptor activation.Histamine and ATP stimulated the release of Ca2+from intracellular Ca2+stores and Ca2+influx across the plasma membrane. Activation of PKC with the phorbol ester β‐phorbol‐12,13 dibutyrate (PDBu; 1 μm) attenuated histamine (100 μm) and ATP (10 μm)‐induced release of intracellular Ca2+and Ca2+influx.The selective PKC inhibitor, Ro 31–8220 (10 μm), reversed the PDBu‐induced attenuation of histamine (100 μm)‐stimulated Ca2+responses.Histamine H1‐ and ATP‐receptors are readily susceptible to homologous desensitization since short‐term exposure to histamine or ATP (450 s) attenuated the Ca2+responses elicited by a second application of the same agonist. Furthermore, H1‐receptor activation‐induced heterologous desensitization of ATP stimulated Ca2+responses andvice versa.Homologous and heterologous desensitization of histamine and ATP Ca2+responses still occurred in the presence of the PKC inhibitor, Ro 31–8220 (10 μm).These data suggest that PKC activation can attenuate histamine H1‐ and ATP‐receptor mediated Ca2+responses. However, based on our experimental data, PKC‐independent mechanisms appear to be involved in the homologous and heterologous desensitization of histamine H1‐ and ATP‐receptor mediated Ca2+responses in DDT1MF‐2 cells.

Bibliography

Dickenson, J. M., & Hill, S. J. (1993). Homologous and heterologous desensitization of histamine H1âand ATPâreceptors in the smooth muscle cell line, DDT1MFâ2: the role of protein kinase C. British Journal of Pharmacology, 110(4), 1449â1456. Portico.

Authors 2

John M. Dickenson (first)
Stephen J. Hill (additional)

References 27 Referenced 30

10.1016/S0021-9258(18)45367-7 / J. Biol. Chem. / Agonist‐dependent phosphorylation of the α2‐adrenergic receptor by the β‐adrenergic receptor kinase by BENOVIC J.L. (1987)
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10.1016/S0021-9258(18)45858-9 / J. Biol. Chem. / Receptor‐activated Ca2+ influx: Two independently regulated mechanisms of influx stimulation coexist in neurosecretory PC12 cells by CLEMENTI E. (1992)
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10.1016/S0026-895X(25)09751-2 / Mol. Pharmacol. / Evidence for alpha‐1 adrenergic receptor internalization in DDT1MF‐2 cells following exposure to agonists plus protein kinase C activators by COWLEN M.S. (1988)
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Dates

Type	When
Created	13 years, 1 month ago (July 20, 2012, 4:06 p.m.)
Deposited	4 months, 3 weeks ago (April 4, 2025, 10:59 p.m.)
Indexed	4 months, 3 weeks ago (April 4, 2025, 11:40 p.m.)
Issued	31 years, 8 months ago (Dec. 1, 1993)
Published	31 years, 8 months ago (Dec. 1, 1993)
Published Online	13 years, 1 month ago (July 19, 2012)
Published Print	31 years, 8 months ago (Dec. 1, 1993)

Funders 0

None

BibTeX

@article{Dickenson_1993, title={Homologous and heterologous desensitization of histamine H1‐and ATP‐receptors in the smooth muscle cell line, DDT1MF‐2: the role of protein kinase C}, volume={110}, ISSN={1476-5381}, url={http://dx.doi.org/10.1111/j.1476-5381.1993.tb13984.x}, DOI={10.1111/j.1476-5381.1993.tb13984.x}, number={4}, journal={British Journal of Pharmacology}, publisher={Wiley}, author={Dickenson, John M. and Hill, Stephen J.}, year={1993}, month=dec, pages={1449–1456} }

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