Purinergic receptors, prostacyclin and atherosclerosis

Ragazzi, Eugenio; Chinellato, Alessandro

doi:10.1016/s1043-6618(05)80125-2

Cited by 3 publications

(3 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This action could occur via the putative P3 receptor. These receptors have been reported to act at presynaptic terminals in the peripheral nervous system to inhibit transmitter release and to be activated both by ATP and adenosine and blocked by methylxanthines (Shinozuka, Bjur & Westfall, 1988; Forsyth, Bjur & Westfall, 1991; Ragazzi & Chinellato, 1992; Todorov, Bjur & Westfall, 1993; Kamiji, Morita & Katayama, 1994). Unfortunately the known pharmacology of these receptors is very limited and thus we cannot distinguish whether the presynaptic effects on ATP release are indeed mediated via an A 2 ‐like receptor with inhibitory actions or rather via a putative P3 receptor.…”

Section: Discussionmentioning

confidence: 99%

ATP and glutamate are released from separate neurones in the rat medial habenula nucleus: frequency dependence and adenosine‐mediated inhibition of release

Robertson

Edwards

1998

The Journal of Physiology

View full text Add to dashboard Cite

ATP and glutamatergic synaptic currents were compared in slices of rat medial habenula nucleus using whole‐cell patch‐clamp techniques. In most cells low voltage stimulation resulted in glutamatergic responses and not purinergic responses. In five cells where ATP currents could be stimulated with low voltages, wash out of glutamate antagonists did not reveal evoked glutamate currents. Spontaneous glutamate currents confirmed washout of antagonist. Modulation of release probability of glutamate and ATP, assessed by changes in failure rate of synaptic currents, was compared under conditions of different stimulation frequencies and in the presence of adenosine agonists and antagonists. ATP release, but not glutamate release, was shown to be modulated by increased stimulation frequency which resulted in inhibition of ATP release via A2‐like adenosine receptors. A1 receptors caused inhibition of both ATP and glutamate release. Endogenous adenosine inhibited glutamate release via A1 receptors but only inhibited ATP release via A2‐like receptors. Attempts to inhibit the degradation of ATP to adenosine did not alter the frequency dependence of the failure rate. We conclude, from the direct demonstration and from the differences in pharmacology and frequency dependence of the modulation of release, that ATP and glutamate responses are due to release from separate neurones.

show abstract

Section: Discussionmentioning

confidence: 99%

ATP and glutamate are released from separate neurones in the rat medial habenula nucleus: frequency dependence and adenosine‐mediated inhibition of release

Robertson

Edwards

1998

The Journal of Physiology

View full text Add to dashboard Cite

show abstract

“…One such stimulus is activation of the erythrocyte prostacyclin (PGI 2 ) receptors (Sprague et al 2008). PGI 2 is released from the endothelium in response to exposure to shear stress and in response to application of ATP in some vascular beds (Ragazzi & Chinellato 1992). The pathway for PGI 2 -mediated ATP release has been well characterized (Fig.…”

Section: Defects In Low-o 2 -Induced Atp Release From Human Erythrocymentioning

confidence: 99%

Role of erythrocyte-released ATP in the regulation of microvascular oxygen supply in skeletal muscle

2015

View full text Add to dashboard Cite

In a 1914 book entitled The Respiratory Function of the Blood, Joseph Barcroft stated that "the cell takes what it needs and leaves the rest." He postulated that there must be both a "call for oxygen" and a "mechanism by which the call elicits a response…" In the past century, intensive investigation has provided significant insights into the hemodynamic and biophysical mechanisms involved in supplying oxygen to skeletal muscle. However, the identification of the mechanism by which tissue oxygen needs are sensed and the affector responsible for altering the upstream vasculature to enable the need to be appropriately met has been a challenge. In 1995, Ellsworth et al proposed that the oxygen carrying erythrocyte, by virtue of its capacity to release the vasoactive mediator ATP in response to a decrease in oxygen saturation, could serve both roles. Several in vitro and in situ studies have established that exposure of erythrocytes to reduced oxygen tension induces the release of ATP which does result in a conducted arteriolar vasodilation with a sufficiently rapid time course to make the mechanism physiologically relevant. The components of the signaling pathway for the controlled release of ATP from erythrocytes in response to exposure to low oxygen tension have been determined. In addition, the implications of defective ATP release on human pathological conditions have been explored. This review provides a perspective on oxygen supply and the role that such a mechanism plays in meeting the oxygen needs of skeletal muscle. Keywords ATP; erythrocyte; Oxygen TransportSkeletal muscle requires not only an adequate convective supply of oxygen (O 2 ) to the muscle as a whole, but also a mechanism to appropriately distribute that O 2 within the muscle to meet localized tissue needs. August Krogh (1919A,B) Based on many decades of research, we know that there must be an effective interaction between the convective and diffusive O 2 transport processes within the microvasculature and the surrounding tissue to ensure a level of tissue oxygenation that meets but, importantly, does not exceed local metabolic needs. The results of experimental studies and computational modeling approaches have resulted in a basic working framework for the process shown in Figure 1. If blood were a simple homogenous fluid, then microvascular blood flow could be easily calculated from knowledge of microvascular architecture (diameter and length of individual vascular segments, and network organization), blood viscosity and the systemic blood pressure gradient across the organ. The Complexities of Basic Microvascular Oxygen TransportMicrovasculature architecture is not static, even in the short term, as regulatory control based on pressure (myogenic control) and flow rate (shear stress) modulate arteriolar diameter while neural, humoral and metabolic regulatory systems attempt to adjust systemic and local microvascular pressure or blood flow. An additional complicating factor is that blood itself is not a homogenous fluid. As the micr...

show abstract

“…The biological relevance for adenine nucleotides acting as autocrine/paracrine signaling molecules is evident by the medley of purinergic receptor subtypes that are differentially expressed across cell types, the extracellular expression of nucleotidases whose activity fine tunes the abundance of ATP outside of the cell and the ubiquitous presence of ATP in all cells in the body, providing a pool of agonist for the initiation of purinergic signaling cascades in all aspects of human physiology. Indeed, purinergic signaling has been implicated in numerous physiological processes, including vascular tone and blood pressure regulation [1][2][3][4][5][6][7], respiratory control [8][9][10], and neurotransmission [11][12][13][14], as well as a number of pathologies including inflammation [15][16][17][18], atherosclerosis [19,20], cancer [21][22][23][24], and neurological disorders [25,26]. Two broad families of purinergic receptors have been identified to date, termed P1 and P2 receptors (for an extensive review on purinergic receptors see [27]).…”

Section: Introductionmentioning

confidence: 99%

Differentiating connexin hemichannels and pannexin channels in cellular ATP release

2014

View full text Add to dashboard Cite

Adenosine triphosphate (ATP) plays a fundamental role in cellular communication, with its extracellular accumulation triggering purinergic signaling cascades in a diversity of cell types. While the roles for purinergic signaling in health and disease have been well established, identification and differentiation of the specific mechanisms controlling cellular ATP release is less well understood. Multiple mechanisms have been proposed to regulate ATP release with connexin (Cx) hemichannels and pannexin (Panx) channels receiving major focus. However, segregating the specific roles of Panxs and Cxs in ATP release in a plethora of physiological and pathological contexts has remained enigmatic. This multifaceted problem has arisen from the selectivity of pharmacological inhibitors for Panxs and Cxs, methodological differences in assessing Panx and Cx function and the potential compensation by other isoforms in gene silencing and genetic knockout models. Consequently, there remains a void in the current understanding of specific contributions of Panxs and Cxs in releasing ATP during homeostasis and disease. Differentiating the distinct signaling pathways that regulate these two channels will advance our current knowledge of cellular communication and aid in the development of novel rationally-designed drugs for modulation of Panx and Cx activity, respectively.

show abstract

Purinergic receptors, prostacyclin and atherosclerosis

Cited by 3 publications

References 43 publications

ATP and glutamate are released from separate neurones in the rat medial habenula nucleus: frequency dependence and adenosine‐mediated inhibition of release

ATP and glutamate are released from separate neurones in the rat medial habenula nucleus: frequency dependence and adenosine‐mediated inhibition of release

Role of erythrocyte-released ATP in the regulation of microvascular oxygen supply in skeletal muscle

Differentiating connexin hemichannels and pannexin channels in cellular ATP release

Contact Info

Product

Resources

About