Effect of Caffeine on Adenosine and Ryanodine Receptor Gene Expression in the Hypothalamus, Pituitary, and Choroid Plexus in Ewes under Basal and LPS Challenge Conditions

Caffeine is a plant alkaloid that stimulates the central nervous system. It easily crosses the blood-brain barrier located in the endothelial cells of brain microvessels and the blood-cerebrospinal fluid barrier located in the epithelial cells of the choroid plexus (ChP). Caffeine exerts most of its biological effects by antagonising adenosine receptors (ADORs), but is also an agonist of ryanodine receptors (RYRs). A recent study in a sheep model has suggested that the effect of caffeine on the expression of many genes may depend on the animal's immune status. Therefore, the aim of the study was to determine the effect of caffeine administration (iv, 30 mg/kg) in ewes, under basal and acute inflammatory conditions induced by lipopolysaccharide injection (iv, 400 ng/kg), on the expression of ADOR and RYR genes in the mediobasal hypothalamus (MBH), anterior pituitary (AP), and ChP. Our study showed that among caffeineinteracting receptors, ADORA1 was the most highly expressed in the AP and ChP, while ADORA3 in the MBH. Caffeine reduced (P < 0.05) the inhibitory effect of inflammation on ADORA1, but only in the MBH, and decreased (P < 0.05) the stimulatory effect of endotoxin treatment on ADORA2B in the MBH and ChP. In contrast to ADORs, the expression of RYRs was less sensitive to the effects of inflammation and caffeine. We showed that caffeine influenced the expression of its receptor genes in the brain, but this effect seemed to be tissuedependent and could be affected by the immune status of the animals. However, the physiological implications of these results require further detailed studies.