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Hormonal dose-response to an adenosine receptor agonist
1Department of Physiology, Faculty of Medicine, Laval University, Québec, Canada.
Canadian Journal of Physiology and Pharmacology
|February 1, 1994
Summary
Adenosine receptor agonist (R)-phenylisopropyladenosine (R-PIA) affects metabolic hormones and stimulates the pituitary-adrenal axis in rats. Higher doses increase glucose and glucagon, while also elevating ACTH and corticosterone.
Area of Science:
- Endocrinology
- Neuroscience
- Pharmacology
Background:
- Adenosine receptors play crucial roles in regulating various physiological processes.
- Adenosine receptor agonists and antagonists have demonstrated effects on metabolic and neuroendocrine functions.
- Previous studies indicated caffeine, an adenosine antagonist, stimulates the pituitary-adrenal axis.
Purpose of the Study:
- To investigate the dose-dependent effects of the adenosine receptor agonist (R)-phenylisopropyladenosine (R-PIA) on plasma levels of key metabolic and hormonal factors.
- To explore the potential influence of R-PIA on glucose, insulin, free fatty acids, glucagon, ACTH, and corticosterone in male rats.
- To elucidate the relationship between adenosine receptor activation and the pituitary-adrenal axis stimulation.
Main Methods:
- Intraperitoneal (i.p.) injection of varying doses of (R)-phenylisopropyladenosine (R-PIA) in male rats (200-g).
- Measurement of plasma levels of free fatty acids, glucose, insulin, glucagon, ACTH, and corticosterone.
- Analysis of dose-response relationships to determine the effects of R-PIA concentrations from nanomolar to micromolar.
Main Results:
- Low doses of R-PIA (0.005 mumol/kg) significantly decreased plasma insulin and free fatty acids.
- Elevated plasma glucose (100% increase) and glucagon were observed at doses of 0.5 mumol/kg and higher, suggesting A2 receptor involvement.
- R-PIA administration at 0.5 mumol/kg and above markedly elevated plasma ACTH and corticosterone, mimicking caffeine's effect on the pituitary-adrenal axis.
Conclusions:
- The adenosine receptor agonist R-PIA exerts significant dose-dependent effects on metabolic parameters and hormonal regulation in rats.
- R-PIA activates the pituitary-adrenal axis, leading to increased ACTH and corticosterone levels, potentially via a centrally mediated mechanism originating from peripheral action.
- Findings suggest a complex interplay between adenosine signaling, metabolic control, and neuroendocrine stress responses.