Pyridoxal 5′-Phosphate is an ATP-Receptor Antagonist in Freshly Isolated Rat Cardiomyocytes

Wang, Xi; Dakshinamurti, K.; Musat, Sorin; Dhalla, Naranjan S.

doi:10.1006/jmcc.1999.0936

Cited by 29 publications

(30 citation statements)

References 3 publications

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“…However, the ATP-induced increases in [Ca 2ϩ ] i were almost completely abolished in cells incubated in Px, indicating that Px is a viable P2 receptor antagonist in murine neuronal cells. This finding is consistent with similar studies in both neuronal cells and in isolated cardiomyocytes (29,43,60), but to our knowledge, this novel finding is the first demonstration in isolated DRG neurons, which are of particular relevance to the EPR.…”

Section: Discussionsupporting

confidence: 93%

“…Px, the chemical precursor of PLP, is a nonselective P2 receptor antagonist (43,51,60) and can be safely administered to humans (24,55). Venous samples were collected to measure plasma PLP, lactate (Accutrend Lactate; Mannheim, Germany), serum potassium (EasyElectrolyte Analyzer; Medica, Bedford, MA), and pH (Accumet Basic AB15; Cole-Parmer, Vernon Hills, IL).…”

Section: In Vivo Human Protocolmentioning

confidence: 99%

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Exaggerated exercise pressor reflex in adults with moderately elevated systolic blood pressure: role of purinergic receptors

Greaney

Matthews

Boggs

et al. 2014

American Journal of Physiology-Heart and Circulatory Physiology

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The neurocirculatory responses to exercise are exaggerated in hypertension, increasing cardiovascular risk, yet the mechanisms remain incompletely understood. The aim of this study was to examine the in vitro effectiveness of pyridoxal-5-phosphate as a purinergic (P2) receptor antagonist in isolated murine dorsal root ganglia (DRG) neurons and the in vivo contribution of P2 receptors to the neurocirculatory responses to exercise in older adults with moderately elevated systolic blood pressure (BP). In vitro, pyridoxal-5-phosphate attenuated the ATP-induced increases in [Ca 2ϩ ]i (73 Ϯ 15 vs. 11 Ϯ 3 nM; P Ͻ 0.05). In vivo, muscle sympathetic nerve activity (MSNA; peroneal microneurography) and arterial BP (Finometer) were assessed during exercise pressor reflex activation (static handgrip followed by postexercise ischemia; PEI) during a control trial (normal saline) and localized P2 receptor blockade (pyridoxal-5-phosphate). Compared with normotensive adults (63 Ϯ 2 yr, 117 Ϯ 2/70 Ϯ 2 mmHg), adults with moderately elevated systolic BP (65 Ϯ 1 yr, 138 Ϯ 5/79 Ϯ 3 mmHg) demonstrated greater increases in MSNA and BP during handgrip and PEI. Compared with the control trial, local antagonism of P2 receptors during PEI partially attenuated MSNA (39 Ϯ 4 vs. 34 Ϯ 5 bursts/min; P Ͻ 0.05) in adults with moderately elevated systolic BP. In conclusion, these data demonstrate pyridoxal-5-phosphate is an effective P2 receptor antagonist in isolated DRG neurons, which are of particular relevance to the exercise pressor reflex. Furthermore, these findings indicate that exercise pressor reflex function is exaggerated in older adults with moderately elevated systolic BP and further suggest a modest role of purinergic receptors in evoking the abnormally large reflex-mediated increases in sympathetic activity during exercise in this clinical population.hypertension; metaboreflex; muscle sympathetic nerve activity; calcium imaging; dorsal root ganglia AUGMENTED PRESSOR RESPONSES to exercise are associated with adverse cardiovascular and cerebrovascular events during and after physical activity (22,34,45). Additionally, nonhypertensive individuals with an exaggerated blood pressure (BP) response to exercise are more likely to develop clinical hypertension (12, 53) and are at higher risk of cardiovascular death compared with those with a normal BP response (57, 61). This risk is further modified by baseline hypertension status (61), making exaggerated BP responses to acute exercise especially problematic in adults with chronically elevated resting BP. Resting systolic BP increases with advancing age, such that ϳ65% of older adults have a resting systolic BP in the high-normal or stage I hypertensive range (i.e., 130 -159 mmHg) (5, 16, 40). Therefore, examining neurocirculatory regulation during exercise in this population is clinically relevant.Muscle contraction causes intensity-dependent increases in arterial BP, heart rate (HR), and sympathetic nerve activity (SNA). Afferent feedback from the exercising skeletal muscle is an import...

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Section: Discussionsupporting

confidence: 93%

Section: In Vivo Human Protocolmentioning

confidence: 99%

Exaggerated exercise pressor reflex in adults with moderately elevated systolic blood pressure: role of purinergic receptors

Greaney

Matthews

Boggs

et al. 2014

American Journal of Physiology-Heart and Circulatory Physiology

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“…In view of the therapeutic potential of PLP for the prevention of ischemic heart disease [ 37 ], it seems appropriate to review the evidence for the action of PLP at the purinergic receptors in the myocardium. By using an isolated perfused heart, an extensive study was undertaken to examine if the positive inotropic effect of ATP was attenuated by PLP [ 58 ]. It was observed that the time-dependent increases in LVDP, + dP/ dt, and -dP/dt by ATP were prevented by pretreatment with PLP.…”

Section: Mechanisms Of Plp Action In the Ischemic Heart Diseasementioning

confidence: 99%

Mechanisms of the beneficial effects of vitamin B6 and pyridoxal 5-phosphate on cardiac performance in ischemic heart disease

Dhalla

Takeda²,

Elimban

2013

Clinical Chemistry and Laboratory Medicine

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Although vitamin B6 and its metabolite, pyridoxal 5 ′ -phosphate (PLP), have been shown to exert bene ficial effects in ischemic heart disease, the mechanisms of their action are not fully understood. Some studies have shown that ventricular arrhythmias and mortality upon the occlusion of coronary artery were attenuated by pretreatment of animals with PLP. Furthermore, ischemia-reperfusion-induced abnormalities in cardiac performance and defects in sarcoplasmic reticular Ca 2 + -transport activities were decreased by PLP. The increase in cardiac contractile activity of isolated heart by ATP was reduced by PLP, unlike propranolol, whereas that by isoproterenol was not depressed by PLP. ATP-induced increase in [Ca ] i in cardiomyocytes was depressed by PLP. Both high-and low-affinity sites for ATP binding in sarcolemmal membranes were also decreased by PLP. These observations support the view that PLP may produce cardioprotective effects in ischemic heart disease by attenuating the occurrence of intracellular Ca 2 + overload due to the blockade of purinergic receptors.

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“…Pyridoxal phosphate had an effect at concentrations equal to those of α, β-methylATP. Wang et al (1999) found that pyridoxal phosphate was an ATP receptor antagonist in rat cardiomyocytes. Binding of 10 μΜ ATP-S to low affinity binding sites was significantly reduced by 1 μΜ pyridoxal phosphate.…”

Section: Pyridoxal Phosphate and Purinoceptorsmentioning

confidence: 99%

“…Binding of 10 μΜ ATP-S to low affinity binding sites was significantly reduced by 1 μΜ pyridoxal phosphate. Wang et al (1999) concluded that since normal plasma concentrations of pyridoxal phosphate range from 24 to 81 nM, pyridoxal phosphate probably would not function as an inhibitor under physiological conditions. However, they also noted that the higher ATP concentrations that were needed in the intact heart and cardiomyocytes than in the sarcolemmal membranes might result from ATP hydrolysis thus suggesting that the effective concentration of ATP might be lower than the administered amount.…”

Section: Pyridoxal Phosphate and Purinoceptorsmentioning

confidence: 99%

Vitamin B-6 Metabolism and Interactions with TNAP

Coburn

2015

Subcellular Biochemistry

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Pyridoxal 5′-Phosphate is an ATP-Receptor Antagonist in Freshly Isolated Rat Cardiomyocytes

Cited by 29 publications

References 3 publications

Exaggerated exercise pressor reflex in adults with moderately elevated systolic blood pressure: role of purinergic receptors

Exaggerated exercise pressor reflex in adults with moderately elevated systolic blood pressure: role of purinergic receptors

Mechanisms of the beneficial effects of vitamin B6 and pyridoxal 5-phosphate on cardiac performance in ischemic heart disease

Vitamin B-6 Metabolism and Interactions with TNAP

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