P1- and P2-purine receptors in brain circulation

As there is increasing evidence that purines are involved in cerebral vasodilatation, purine receptors were characterized pharmacologically in pial arteries from rabbit, cat and man, and compared with purine receptors in various non-cerebral vascular beds. Use of agonists and antagonists allows purine receptors to be divided into P1 and P2 receptors. The location of these receptors on the surface of the various cells in the cerebrovascular wall was determined. P1 receptors, stimulated primarily by adenosine, are located on the smooth muscle cells, causing relaxation. P2 receptors, stimulated primarily by ADP and ATP, are located on endothelial cells and cause relaxation, and are also found on smooth muscle cells where they cause contraction. Slowly degradable ATP analogues were considerably more potent constrictors than ATP but not equally potent as dilators, which might indicate minor differences between the P2 receptors on smooth muscle and on endothelium. The P1 receptor was further subclassified into the A2 type. Adenosine may also reach an intracellular purine receptor, via an uptake process, to cause additional relaxation, as was shown with an intracellular purine receptor agonist in cat pial arteries. Brain vessels were found to be considerably more sensitive to purines than most non-cerebral vessels studied.