Spatial aspects of intracellular pH regulation in heart muscle

Vaughan‐Jones, Richard D.; Spitzer, Kenneth W.; Swietach, Pawel

doi:10.1016/j.pbiomolbio.2005.06.004

Cited by 42 publications

(30 citation statements)

References 52 publications

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“…The increase in muscle CAR content was expected to enhance intramuscular hydrogen ion (H ? ) buffering capacity (Vaughan-Jones et al 2006). Indeed, exercise-induced acidosis was attenuated by chronic treatment of b-alanine, which increased muscle CAR content (Baguet et al 2010).…”

Section: Carnosine Synthetase and Carnosinasementioning

confidence: 97%

Role of l-carnosine in the control of blood glucose, blood pressure, thermogenesis, and lipolysis by autonomic nerves in rats: involvement of the circadian clock and histamine

et al. 2012

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L-carnosine (β-alanyl-L-histidine; CAR) is synthesized in mammalian skeletal muscle. Although the physiological roles of CAR have not yet been clarified, there is evidence that the release of CAR from skeletal muscle during physical exercise affects autonomic neurotransmission and physiological functions. In particular, CAR affects the activity of sympathetic and parasympathetic nerves innervating the adrenal glands, liver, kidney, pancreas, stomach, and white and brown adipose tissues, thereby causing changes in blood pressure, blood glucose, appetite, lipolysis, and thermogenesis. CAR-mediated changes in neurotransmission and physiological functions were eliminated by histamine H1 or H3 receptor antagonists (diphenhydramine or thioperamide) and bilateral lesions of the hypothalamic suprachiasmatic nucleus (SCN), a master circadian clock. Moreover, a carnosine-degrading enzyme (carnosinase 2) was shown to be localized to histamine neurons in the hypothalamic tuberomammillary nucleus (TMN). Thus, CAR released from skeletal muscle during exercise may be transported into TMN-histamine neurons and hydrolyzed. The resulting L-histidine may subsequently be converted into histamine, which could be responsible for the effects of CAR on neurotransmission and physiological function. Thus, CAR appears to influence hypoglycemic, hypotensive, and lipolytic activity through regulation of autonomic nerves and with the involvement of the SCN and histamine. These findings are reviewed and discussed in the context of other recent reports, including those on carnosine synthetases, carnosinases, and carnosine transport.

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Section: Carnosine Synthetase and Carnosinasementioning

confidence: 97%

Role of l-carnosine in the control of blood glucose, blood pressure, thermogenesis, and lipolysis by autonomic nerves in rats: involvement of the circadian clock and histamine

et al. 2012

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“…This equilibration is performed with constraints to prevent PT; these are subsequently released. These comprise harmonic restraints for the O A −H A and O A ⋯N separations at 1 and 2.9 Å respectively, with a spring constant of 10 kcal/mol/Å 2 for each. These separations help to ensure that the surrounding water solvent molecules are in a configuration that does not favor PT, that is, that favors the neutral pair reactant (cf.…”

Section: Simulation Detailsmentioning

confidence: 99%

Reaction Mechanism for Direct Proton Transfer from Carbonic Acid to a Strong Base in Aqueous Solution I: Acid and Base Coordinate and Charge Dynamics

et al. 2016

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Protonation by carbonic acid H2CO3 of the strong base methylamine CH3NH2 in a neutral contact pair in aqueous solution is followed via Car–Parrinello molecular dynamics simulations. Proton transfer (PT) occurs to form an aqueous solvent-stabilized contact ion pair within 100 fs, a fast time scale associated with the compression of the acid–base hydrogen-bond (H-bond), a key reaction coordinate. This rapid barrierless PT is consistent with the carbonic acid-protonated base pKa difference that considerably favors the PT, and supports the view of intact carbonic acid as potentially important proton donor in assorted biological and environmental contexts. The charge redistribution within the H-bonded complex during PT supports a Mulliken picture of charge transfer from the nitrogen base to carbonic acid without altering the transferring hydrogen’s charge from approximately midway between that of a hydrogen atom and that of a proton.

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“…5). The latter is interesting since several cardiac effects have been reported for carnosine including increased calcium release via the ryanodine receptors leading to elevations in contractility compared to control [28] and a role in intracellular proton diffusion [25]. The possible usefulness that the cardiomyocyte transporter may offer as a target for drug delivery was demonstrated with Least squares analysis was used to fit the data to the best straight line.…”

Section: Discussionmentioning

confidence: 99%

“…In the choroid plexus, it has been suggested that PEPT2 mediates the efflux of brain-derived peptides from the cerebrospinal fluid into the blood [20]. In cardiomyocytes, absorption or secretion via PEPT2 may help to preserve the intracellular dipeptide pool for use in intracellular proton diffusion [25]. Alternatively, PEPT2 might be involved in glutathione cycling and synthesis, as suggested for astroglial cells [5].…”

Section: Discussionmentioning

confidence: 99%

Demonstration of functional dipeptide transport with expression of PEPT2 in guinea pig cardiomyocytes

Lin

King

2006

Pflugers Arch - Eur J Physiol

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The transporters PEPT1 and PEPT2 accept a broad spectrum of substrates including small, naturally occurring peptides and peptidomimetic drugs. This study aimed to investigate for the first time whether these transporters are expressed and active in isolated cardiomyocytes. PEPT1/PEPT2 expression in rat kidney (positive control), guinea pig kidney and cardiomyocytes were investigated by reverse transcription polymerase chain reaction. L-Glycyl-L-[(14)C]sarcosine (Gly-sar) uptake was characterised using freshly isolated suspensions of adult male guinea pig cardiomyocytes. PEPT2-specific primers recognised mRNA of appropriate size and sequence in cardiomyocytes and kidney, whilst PEPT1 was expressed in the kidney only. The initial uptake (30 s) of 200 microM Gly-sar was dependent on extracellular pH with a maximum at pH 6.0 (237.8 +/- 12.2 pmol/microl) and a minimum at pH 8.0 (72.1 +/- 13.4 pmol/microl, n = 6 +/- SE, p < 0.01, T test). The K (m) and V (max) of Gly-sar uptake at pH 6.0 were 495.5 +/- 69.6 microM and 1470.5 +/- 69.6 pmol microl(-1) min(-1). The addition of 10 mM fosinopril, cefadroxil, carnosine, cyclacillin or a variety of L-amino acid containing dipeptides/tripeptides significantly reduced Gly-sar uptake. Gly-sar uptake was not affected by 10 mM D-ala-D-ala, glycine or sarcosine. These results support the presence of a functional dipeptide transporter in isolated cardiomyocytes, with accompanying expression of PEPT2.

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Spatial aspects of intracellular pH regulation in heart muscle

Cited by 42 publications

References 52 publications

Role of l-carnosine in the control of blood glucose, blood pressure, thermogenesis, and lipolysis by autonomic nerves in rats: involvement of the circadian clock and histamine

Role of l-carnosine in the control of blood glucose, blood pressure, thermogenesis, and lipolysis by autonomic nerves in rats: involvement of the circadian clock and histamine

Reaction Mechanism for Direct Proton Transfer from Carbonic Acid to a Strong Base in Aqueous Solution I: Acid and Base Coordinate and Charge Dynamics

Demonstration of functional dipeptide transport with expression of PEPT2 in guinea pig cardiomyocytes

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