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.

P2X Receptor Immunoreactivity in Different Arteries from the Femoral, Pulmonary, Cerebral, Coronary and Renal Circulations

“…Immunoreactivity for P2X 4 receptors was also detected in all the arteries tested. Our results extend the range of arteries in which P2X 1 and P2X 4 receptors have been detected [17, 18, 24, 25, 28, 30, 31, 32, 33]. At high-power magnification, immunoreactivity for both P2X 1 and P2X 4 receptors had a punctate distribution indicative of receptor clustering.…”

“…In the majority of arteries, including ear, cerebral, mesenteric, pulmonary and coronary arteries, the desensitising nature of P2X receptor-mediated currents [21, 23, 43, 44, 45]and the sensitivity of contractile responses to the agonist α,β-meATP (EC 50 approximately 1 µ M ) [3, 23, 30, 41, 46, 47, 48]are indistinguishable from the properties of recombinant homomeric P2X 1 receptors [49]. There is no evidence to suggest that homomeric P2X 4 and P2X 5 or heteromeric P2X 1/5 receptors contribute to P2X receptor currents in arteries, as a characteristic property of these recombinant receptors are non-desensitising components to the P2X receptor currents [26, 50, 51, 52].…”

Peripheral sensitization in migraine—role for P2X purinergic receptors in the dura–vascular sensory pathway

“…Messenger RNA for all members of the P2X receptor family (and some members of the P2Y family) is present in the smooth muscle of rat pial arterioles and ATP induces a transient vasoconstriction through P2X 1 receptors [Lewis et al, 2000]. P2X 1 receptor protein is present on human cerebral arteries, which contract in response to a,b-meATP [Bo et al, 1998]. Other recent studies give support to this hypothesis.…”

“…As discussed above, ATP appears to act through P2Y receptors on the peripheral terminals of trigeminal afferents [Zimmermann et al, 2002], through P2X 7 receptors on the mast cells [Bulanova et al, 2005] and directly on blood vessels, through P2X 1 receptors [Bo et al, 1998;Lewis et al, 2000]. P2X 3 and P2X 2/3 receptors have been shown to mediate central sensitization in the trigeminal system as discussed above [Chiang et al, 2005].…”

Dexamethasone Alters Vascular Reactivity by Enhancing COX-Related Vasodilatation in Fetal Ovine Carotids

“…Although endothelial responses usually decrease 8 h after death, dose-dependent contractions have been documented in human arteries obtained at 37-54 h postmortem [15,16] . All procedures were reviewed and approved by the Institutional Review Board of Loma Linda University and Loma Linda University Medical Center.…”