The Characteristics and Distribution of α2D-, α2B- and α2C-Adrenoceptor Subtypes in Goats.

Ming Xu,Qi Wang,Mingxing Ding,Di Pan,Qiulin Zhang,Yi Ding

doi:10.3390/ani12050664

Abstract

Simple Summaryα2-Adrenergic receptors mediate many diverse biological effects of the endogenous catecholamines epinephrine and norepinephrine. Three distinct subtypes of α2-adrenergic receptors, α2B, α2C and α2D, have been identified in goats; however, the characteristics and distribution of α2-adrenoceptors in goats remain unclear. Therefore, the aim of our study was to assess the characteristics and distribution of α2-adrenoceptor subtypes in goats. Our study highlights the wide but uneven distribution of α2-adrenoceptor subtypes in goats. Additionally, our study showed that α2D-ceptor has a better analgesic effect in goats than α2B- and α2C-adrenoceptor, whereas α2C-adrenoceptor plays a more important role in thermoregulation than α2B- and α2D-adrenoceptors.α2-Adrenegic receptors (α2Rs) are important presynaptic modulators of central noradrenergic function (auto receptors) and postsynaptic mediators of many of the widespread effects of catecholamines and related drugs. Studies have shown that ruminants (such as goats and cattle) express special α2DR subtypes in addition to α2BR and α2CR. Real-time quantitative PCR and Western blotting were used to investigate the distribution and density of α2R in different nuclei of the goat central nervous system, selected regions of the spinal cord (L4-L6), and in various peripheral tissues. α2-AR subtype-specific antibodies were injected intrathecally and intracerebroventricularly into the tested goats to block the corresponding subtype of receptors. Pain threshold and physiological parameters were evaluated to explore the functional characteristics of α2BR, α2CR and α2DR in goats. Our results suggest that the expression of the mRNAs and proteins of all three α2R subtypes are widely but unevenly distributed in the goat CNS and peripheral tissues. Furthermore, α2DR plays a more important role in α2R-mediated analgesia in goats than α2BR and α2CR, whereas α2CR activation exerts a greater effect on body temperature than α2BR and α2DR.

Highlights

Supraspinal sites are involved in α2-Adrenegic receptors (α2Rs) agonist-mediated analgesic effects; Peng et al indicated that α2-Adrenergic receptor (α2R) in the periventricular gray is important for suppressing pain using the cell clamp technique [11]
The levels of the α2DR, α2BR and α2CR mRNAs were detected in different nuclei and regions in the CNS and peripheral tissues of goats to assess the distribution of α2DR, α2BR and α2CR in the CNS and peripheral tissues in goats (Figure 2)
Our results showed a distinct expression pattern of α2R subtypes in different areas of the vascular system. α2BR is the major subtype expressed in myocardium. α2DR is predominantly expressed in aortas and arterioles, whereas α2CR is mainly expressed in the vena cava and venules of goats

Summary

Introduction

Introduction α2-Adrenergic receptor (α2R) agonists are some of the most commonly used sedative analgesic drugs in veterinary medicine due to their availability, reversibility and rapid onset [1–3] This class of drugs is commonly used as a premedication to sedate animals or as an anesthetic adjuvant to reduce the side effects of other drugs. Kästner et al reported that an α2R agonist activates pulmonary intravascular macrophages (PIMs), a specialized group of macrophages found in ruminants, which are capable of producing a range of vasoactive mediators and cytokines [14] One study showed the rapid onset of arterial hypoxemia and its complete reversal by al-pha antagonists given before or within the first 5 min after xylazine administration [15], indicating that functional changes such as vasoconstriction and the redistribution of blood flow are responsible for the first stage of impaired oxygenation. We described the distribution, density and functional characters of α2R subtypes in goats, which would help develop α2R subtype-specific agonists that are more effective in analgesia and sedation, and exert fewer side effects on ruminants

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