P2X purinoceptors in postmortem human cerebral arteries.

Abstract

Pharmacological studies have demonstrated that various purinoceptors are involved in the control of the cerebral vascular tone in many species. In this study, the existence of P2X purinoceptors in the postmortem human cerebral arteries was investigated with organ-bath pharmacology, autoradiography, and immunohistochemistry. Specimens were obtained from the M2 region of the middle cerebral arteries from human cadavers with an age range of 53-91 years and postmortem time of 37-54 h. Application of alpha,beta-methylene adenosine triphosphate (ATP) produced concentration-dependent contraction in the arterial ring, whereas transmural nerve stimulation and noradrenaline did not elicit contraction. Autoradiography using [3H]alpha,beta-methylene ATP (a radioligand for P2X purinoceptors) showed specific [3H]alpha,beta-methylene ATP binding sites in the smooth-muscle cells of the postmortem human cerebral arteries. Immunohistochemistry with specific P2X1 purinoceptor antibodies revealed positive staining exclusively in the smooth muscle of the same specimens. All these results demonstrate the existence of P2X purinoceptors in human cerebral arteries, which were still functionally active despite the long postmortem time. The results from this study suggest that the postmortem human cerebral arteries can be useful specimens for studying the P2X purinoceptor-mediated responses.