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Adrenergic receptors: biphasic dose responses.

E J Calabrese1

  • 1Department of Environmental Health Sciences, School of Public Health and Health Sciences, University of Massachusetts, Amherst 01003, USA. edwardc@schoolph.umass.edu

Critical Reviews in Toxicology
|August 16, 2001
PubMed
Summary

Adrenergic receptor agonists and antagonists commonly exhibit U-shaped dose responses across various biological endpoints. These biphasic effects, observed in smooth muscle, memory, and blood pressure, have mechanistic underpinnings.

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Area of Science:

  • Pharmacology and Physiology
  • Adrenergic Receptor System Research

Background:

  • The adrenergic receptor system plays a crucial role in regulating numerous physiological processes.
  • Understanding dose-response relationships is fundamental to pharmacology and drug development.

Purpose of the Study:

  • To investigate the dose-response relationships of adrenergic receptor agonists and antagonists.
  • To characterize the prevalence and nature of U-shaped (biphasic) dose responses across diverse biological models and endpoints.

Main Methods:

  • Systematic assessment of adrenergic receptor modulators across various biological models, tissues, and endpoints.
  • Analysis of dose-response curves to identify patterns, including biphasic responses.
  • Mechanistic investigations for selected biphasic dose responses.

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Main Results:

  • U-shaped dose-response relationships were frequently observed, impacting endpoints like smooth muscle function, memory, blood pressure, sexual behavior, and platelet aggregation.
  • Mechanistic explanations for biphasic responses were established in six studied endpoints.
  • Maximum stimulatory responses were typically less than twofold above control levels, with a 10- to 1000-fold range, except for platelet aggregation (10^3 to 10^5-fold).

Conclusions:

  • Biphasic dose-response relationships are a common characteristic of adrenergic receptor modulation across a wide array of physiological functions.
  • The quantitative features of these responses provide insights into receptor system sensitivity and regulatory mechanisms.
  • Further research into the mechanisms underlying these biphasic effects can inform therapeutic strategies involving adrenergic agents.