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Pulmonary pharmacology & therapeutics2020; 61; 101897; doi: 10.1016/j.pupt.2020.101897

Presence and function of β-adrenergic receptors in primary equine bronchial epithelia cells.

Abstract: The β-adrenergic receptor (β-AR) plays an important role in regulating a variety of cell and organ functions in different animal species and is an important target in asthma pathogenesis and therapy. The β-AR expression and function in equine bronchial epithelial cells (EBEC) were not known but innervation and significant decrease in receptor level were reported in the equine bronchial tissues from asthmatic horses. I-iodocyanopindolol (ICYP) binding studies were undertaken in primary freshly isolated and cultured EBEC to identify the presence of the β-ARs. The receptor distribution was assessed using subtype-selective β-AR antagonists (ICI 118 551 (β) and CGP 20712A (β). The β-AR function was confirmed by measuring the agonist-induced intracellular cAMP accumulation in freshly isolated and cultured EBEC. In both freshly isolated and cultured EBEC, the specific ICYP binding was saturable and of high affinity. The maximal receptor density (B) was 9763 ± 140 binding sites/cell (mean ± SEM, n = 7) and 10575 ± 194 binding sites/cell (mean ± SEM, n = 5) in freshly isolated and cultured EBEC, respectively. The receptor affinity to the ligand (K) was also not different between the two cell conditions. ICI 118.551 displaced ICYP with 25 000-fold higher affinity than CGP 20712A. Moreover, in both fresh isolated and cultured EBEC, cAMP-accumulation was stimulated with a rank-order of potency of isoproterenol > adrenaline > noradrenaline. These results highlight the β-AR to be a key subtype in both freshly isolated and cultured primary EBEC.
Publication Date: 2020-01-18 PubMed ID: 31962137DOI: 10.1016/j.pupt.2020.101897Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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This research paper analyzes the presence and function of β-adrenergic receptors in primary equine bronchial epithelial cells and their potential use in asthma pathology and therapy.

Introduction

The paper seeks to address the gap in knowledge regarding the presence and function of β-adrenergic receptors (β-ARs) in primary equine bronchial epithelial cells (EBEC). The β-AR is known to play a significant role in regulating cell and organ functions in various animal species, and it is also an important target in asthma detection and treatment processes.

Methodology

  • The researchers conducted I-iodocyanopindolol (ICYP) binding studies on freshly isolated and cultured EBEC to determine the presence of β-ARs.
  • They evaluated receptor distribution using β-AR antagonists (ICI 118 551 (β) and CGP 20712A (β)).
  • To verify the function of the β-AR, the scientists measured the accumulation of an intracellular messenger molecule, cyclic AMP (cAMP), in both freshly isolated and cultured EBEC following exposure to an agonist, a substance triggering a response in the receptor.

Findings

  • β-AR was found in both freshly isolated and cultured EBEC, with the ICYP binding showing high affinity and saturability.
  • The maximum receptor density or B-max values were determined to be 9763 ± 140 binding sites/cell (mean ± SEM, n = 7) and 10575 ± 194 binding sites/cell (mean ± SEM, n = 5) for freshly isolated and cultured EBEC, respectively.
  • No difference was observed in the receptor affinity towards the ligand between the two cell conditions, defined by the dissociation constant, Kd.
  • The antagonist ICI 118.551 was found to displace ICYP with a significantly higher affinity, about 25,000 times more, than CGP 20712A.
  • cAMP accumulation was found to be stimulated in both types of cells, with isoproterenol showing the highest effectiveness, followed by adrenaline and noradrenaline successively.

Implications

These results indicate that the β-AR is a predominant subtype present in freshly isolated and cultured primary EBEC. The findings also provide a basis for further studies investigating the role of β-AR in equine asthma pathogenesis and its potential use in asthma therapy.

Cite This Article

APA
Schellenberg LM, Bonicelli J, Hochheim I, Regenthal R, Abraham G. (2020). Presence and function of β-adrenergic receptors in primary equine bronchial epithelia cells. Pulm Pharmacol Ther, 61, 101897. https://doi.org/10.1016/j.pupt.2020.101897

Publication

ISSN: 1522-9629
NlmUniqueID: 9715279
Country: England
Language: English
Volume: 61
Pages: 101897
PII: S1094-5539(19)30074-4

Researcher Affiliations

Schellenberg, Linda Marie
  • University of Leipzig, Faculty of Veterinary Medicine, Institute of Pharmacology, Pharmacy and Toxicology, An den Tierkliniken 15, 04103, Leipzig, Germany.
Bonicelli, Jana
  • University of Leipzig, Faculty of Veterinary Medicine, Institute of Pharmacology, Pharmacy and Toxicology, An den Tierkliniken 15, 04103, Leipzig, Germany.
Hochheim, Ina
  • University of Leipzig, Faculty of Veterinary Medicine, Institute of Pharmacology, Pharmacy and Toxicology, An den Tierkliniken 15, 04103, Leipzig, Germany.
Regenthal, Ralf
  • Rudolf-Boehm-Institute of Pharmacology and Toxicology, Clinical Pharmacology, Faculty of Medicine, Leipzig University, Leipzig, Germany. Electronic address: ralf.regenthal@medizin.uni-leipzig.de.
Abraham, Getu
  • University of Leipzig, Faculty of Veterinary Medicine, Institute of Pharmacology, Pharmacy and Toxicology, An den Tierkliniken 15, 04103, Leipzig, Germany. Electronic address: gabraham@rz.uni-leipzig.de.

MeSH Terms

  • Adrenergic beta-Antagonists / metabolism
  • Animals
  • Bronchi / metabolism
  • Cells, Cultured
  • Cyclic AMP / metabolism
  • Epithelial Cells / metabolism
  • Horses
  • Imidazoles / metabolism
  • Iodocyanopindolol / metabolism
  • Isoproterenol / pharmacology
  • Primary Cell Culture
  • Propanolamines / metabolism
  • Receptors, Adrenergic, beta / metabolism
  • Receptors, Adrenergic, beta-1 / metabolism
  • Receptors, Adrenergic, beta-2 / metabolism

Conflict of Interest Statement

Declaration of competing interest None.

Citations

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