Polarized distribution of bradykinin receptors on airway epithelial cells and independent coupling to second messenger pathways

G M Denning; M J Welsh

doi:10.1016/S0021-9258(18)98784-3

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Polarized distribution of bradykinin receptors on airway epithelial cells and independent coupling to second messenger pathways

Journal article

Open access

Peer reviewed

Polarized distribution of bradykinin receptors on airway epithelial cells and independent coupling to second messenger pathways

G M Denning and M J Welsh

The Journal of biological chemistry, Vol.266(20), pp.12932-12938

07/15/1991

DOI: 10.1016/S0021-9258(18)98784-3

PMID: 1649170

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Abstract

Bradykinin stimulates Cl- secretion by airway epithelia, but different patterns of secretion result from addition to the mucosal and submucosal surfaces. Earlier work suggested that bradykinin activates two second messenger pathways: increasing inositol phosphates (InsP) via phosphatidylinositol bisphosphate hydrolysis and increasing cAMP via arachidonic acid metabolism. In this study, we measured arachidonic acid release and InsP production in cultured canine tracheal epithelial cells. Bradykinin increased the two second messengers via independent mechanisms: (a) dose-response curves with different incubation media demonstrated that each second messenger could be generated independently of the other; (b) phorbol ester inhibited InsP production but stimulated arachidonic acid release; (c) for polarized cultures, submucosal bradykinin stimulated production of both second messengers but mucosal bradykinin stimulated only arachidonic acid release. To determine if differences in second messenger formation at the two membranes resulted from differences in hormone-receptor interactions, we compared bradykinin binding to the apical and basolateral membranes. Both the binding capacities and affinity constants (KD) were different (basolateral KD, 257 +/- 53 pM; apical KD, 39 +/- 3 pM). These data demonstrate polarized coupling of bradykinin receptors to second messenger pathways in airway epithelial cells and suggest that this polarized coupling is due to different bradykinin receptors at the two membranes.

Epithelium - drug effects

Guanosine 5'-O-(3-Thiotriphosphate) - pharmacology

Second Messenger Systems - drug effects

Bradykinin - metabolism

Tetradecanoylphorbol Acetate - pharmacology

Epithelium - metabolism

Cells, Cultured

Receptors, Neurotransmitter - drug effects

Trachea - metabolism

Receptors, Neurotransmitter - physiology

Arachidonic Acids - metabolism

Animals

Receptors, Bradykinin

Dogs

Cell Membrane - metabolism

Receptors, Neurotransmitter - metabolism

Kinetics

Inositol Phosphates - metabolism

Arachidonic Acid

Bradykinin - pharmacology

Cell Membrane - drug effects

Details

Title: Subtitle: Polarized distribution of bradykinin receptors on airway epithelial cells and independent coupling to second messenger pathways
Creators: G M Denning - Howard Hughes Medical Institute, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242
M J Welsh
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.266(20), pp.12932-12938
DOI: 10.1016/S0021-9258(18)98784-3
PMID: 1649170
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: United States
Grant note: HL 42385 / NHLBI NIH HHS
Language: English
Date published: 07/15/1991
Academic Unit: Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Emergency Medicine; Fraternal Order of Eagles Diabetes Research Center; Neurosurgery; Internal Medicine
Record Identifier: 9984020876002771

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