Background: [alpha]2-Adrenergic receptor ([alpha]2AR) agonists have become Important adjuncts as anesthetic agents. They act by binding to [alpha]2ARs on the surface of cell membranes and cause centrally mediated sedation and analgesia. [alpha]2ARs also contribute to other aspects of physiologic regulation. Three subtypes of [alpha]2ARs ([alpha]2-c2, [alpha]2-c4, and [alpha]2-c10) have been described using molecular and pharmacologic techniques. We recently demonstrated species heterogeneity in the distribution of [alpha]1-adrenergic receptor subtypes, therefore making it imperative to analyze the distribution of [alpha]2AR subtypes in human tissues. This information may have importance in the understanding of potential side effects of administration of [alpha]2AR subtype-selective agonists for anesthesia In humans.
Methods: RNA extracted from human tissues was analyzed by using quantitative ribonuclease protection assays to determine [alpha]2AR subtype messenger RNA (mRNA) expression in cardiovascular, central nervous system, and peripheral tissues.
Results: [alpha]2AR mRNA is present in greatest concentrations in human kidney, followed by aorta > spleen > heart = lung. [alpha]2-c4 mRNA predominates in heart, lung, aorta, cerebral cortex, cerebellum, spleen, kidney, and adrenal gland; [alpha]2-c2 mRNA in liver; and [alpha]2-c10 mRNA in pancreas and small intestine. Hence [alpha]2AR subtype mRNA distribution is tissue-selective and differs from that reported for rat.
Conclusions: (1) On comparison with previous research we find possible species heterogeneity in [alpha]2AR subtype mRNA distribution (rat vs. human) for all three [alpha]2AR subtypes. (2) We demonstrate the presence and subtype heterogeneity of [alpha]2AR subtype mRNA in both brain and peripheral tissues. (3) Significant concentrations of [alpha]2AR mRNA are present in adult human heart. These findings have Important Implications for our understanding of human adrenergic physiology, provide a possible explanation for the existence of pharmacologically similar yet distinct [alpha]2AR subtypes, and may be important for the rational development of [alpha]2AR subtype-selective anesthetics and other therapeutic agents for use in treating human diseases.
(C) 1994 American Society of Anesthesiologists, Inc.