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Changes in adenosine receptors mediating hypotension in morphine-dependent rats
P J White1, R B Rose'Meyer, W Hope
1Department of Pharmaceutical Biology and Pharmacology, Monash University, Parkville, Victoria, Australia.
European Journal of Pharmacology
|December 27, 1995
Summary
Morphine dependence alters blood pressure regulation by adenosine receptors. Studies in rats show adenosine A1 receptors are downregulated, while adenosine A2A receptors are upregulated, affecting hypotensive responses.
Area of Science:
- Pharmacology
- Neuroscience
- Cardiovascular Physiology
Background:
- Morphine's hypotensive effects are mediated by adenosine.
- Tolerance to morphine's hypotensive effects is known.
- Morphine dependence may alter adenosine receptor function.
Purpose of the Study:
- To investigate if morphine dependence alters adenosine receptor-mediated blood pressure changes in rats.
- To examine the roles of adenosine A1 and A2A receptors in morphine-dependent rats.
Main Methods:
- Induction of morphine dependence in Hooded Wistar rats.
- Administration of adenosine receptor agonists and antagonists in intact and pithed rat preparations.
- Measurement of blood pressure responses to pharmacological agents.
Main Results:
- Adenosine's hypotensive effects were reduced in morphine-dependent rats.
- Adenosine A1 receptor agonist effects were diminished, while A2A receptor agonist effects were enhanced in dependent rats (intact prep).
- In pithed rats, both agonists had greater effects in dependent rats, and antagonist potencies were unchanged.
Conclusions:
- Morphine dependence leads to downregulation of adenosine A1 receptors.
- Morphine dependence results in upregulation of adenosine A2A receptors.
- These receptor alterations contribute to modified cardiovascular responses in morphine dependence.