Muscarinic mobilization of choline in rat cerebral cortex does not involve alterations of blood-brain barrier

Brehm, R.; Corradetti, Renato; Krahn, V; Löffelholz, K.; Pepeu, Giancarlo

doi:10.1016/0006-8993(85)91007-8

Cited by 15 publications

(4 citation statements)

References 22 publications

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“…The relationships between acetylcholine synthesis and phospholipid metabolism, however, are not well understood. We have previously obtained evidence that muscarink receptor stimulation leads to increased choline release from choline-containing phospholipids (Brehm et al, 1985(Brehm et al, , 1987Loffelholz, 1989a,b). The present data indicate that the mobilization of temporarily stored choline from bound stores may be more important for the continuous supply of choline for acetylcholine synthesis than the free extracellular choline which has been taken up very recently from the blood.…”

Section: Fate Of Newly Taken Up Brain Cholinementioning

confidence: 99%

Small Rises in Plasma Choline Reverse the Negative Arteriovenous Difference of Brain Choline

Klein

Köppen

Löffelholz

1990

Journal of Neurochemistry

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The concentrations of free choline in blood plasma from a peripheral artery and from the transverse sinus, in the CSF, and in total brain homogenate, have been measured in untreated rats and in rats after acute intraperitoneal administration of choline chloride. In untreated rats, the arteriovenous difference of brain choline was related to the arterial choline level. At low arterial blood levels (less than 10 microM) as observed under fasting conditions, the arteriovenous difference was negative (about -2 microM), indicating a net release of choline from the brain of about 1.6 nmol/g/min. In rats with spontaneously high arterial blood levels (greater than 15 microM), the arteriovenous difference was positive, implying a marked net uptake of choline by the brain (3.1 nmol/g/min). The CSF choline concentration, which reflects changes in the extracellular choline concentration, also increased with increasing plasma levels and closely paralleled the gradually rising net uptake. Acute administration of 6, 20, or 60 mg of choline chloride/kg caused, in a dose-dependent manner, a sharp rise of the arterial blood levels and the CSF choline, and reversed the arteriovenous difference of choline to markedly positive values. The total free choline in the brain rose only initially and to a quantitatively negligible extent. Thus, the amount of choline taken up by the brain within 30 min was stored almost completely in a metabolized form and was sufficient to sustain the release of choline from the brain as long as the plasma level remained low. We conclude that the extracellular choline concentration of the brain closely parallels fluctuations in the plasma level of choline.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Fate Of Newly Taken Up Brain Cholinementioning

confidence: 99%

Small Rises in Plasma Choline Reverse the Negative Arteriovenous Difference of Brain Choline

Klein

Köppen

Löffelholz

1990

Journal of Neurochemistry

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“…Parallel formations of PA and choline as a consequence of PLD-stimulated PC hydrolysis have been demonstrated in chicken heart muscle [5], rat cerebral cortex [9,25] and 1321N1 astrocytoma cells [1]. In addition, direct activation of protein kinase C (PKC) in many cells and tissues by tumor-promoting phorbol esters such as phorbol 12-myristate 13-acetate (PMA) has been found to stimulate PLD activity and the response has been demonstrated to be sensitive to PKC inhibitors [24].…”

Section: Figmentioning

confidence: 99%

“…There is evidence that parallel formation of PA and choline in stimulated tissue occurs, leading to the hypothesis that activation of the mAChR stimulates PC hydrolysis by activating PLD [5]. Parallel formations of PA and choline as a consequence of PLD-stimulated PC hydrolysis have been demonstrated in chicken heart muscle [5], rat cerebral cortex [9,25] and 1321N1 astrocytoma cells [1].…”

Section: Figmentioning

confidence: 99%

Activation of Muscarinic Receptors in Porcine Airway Smooth Muscle Elicits a Transient Increase in Phospholipase D Activity

et al. 1999

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Phospholipase D (PLD) is a phosphodiesterase that catalyses hydrolysis of phosphatidylcholine to produce phosphatidic acid and choline. In the presence of ethanol, PLD also catalyses the formation of phosphatidylethanol, which is a unique characteristic of this enzyme. Muscarinic receptor-induced changes in the activity of PLD were investigated in porcine tracheal smooth muscle by measuring the formation of [³H]phosphatidic acid ([³H]PA) and [³H]phosphatidylethanol ([³H]PEth) after labeling the muscle strips with [³H]palmitic acid. The cholinergic receptor agonist acetylcholine (Ach) significantly but transiently increased formation of both [³H]PA and [³H]PEth in a concentration-dependent manner (>105–400% vs. controls in the presence of 10^–6 to 10^–4 M Ach) when pretreated with 100 mM ethanol. The Ach receptor-mediated increase in PLD activity was inhibited by atropine (10^–6 M), indicating that activation of PLD occurred via muscarinic receptors. Activation of protein kinase C (PKC) by phorbol-12-myristate-13-acetate (PMA) increased PLD activity that was effectively blocked by the PKC inhibitors calphostin C (10^–8 to 10^–6 M) and GFX (10^–8 to 10^–6 M). Ach-induced increases in PLD activity were also significantly, but incompletely, inhibited by both GFX and calphostin C. From the present data, we conclude that in tracheal smooth muscle, muscarinic acetylcholine receptor-induced PLD activation is transient in nature and coupled to these receptors via PKC. However, PKC activation is not solely responsible for Ach-induced activation of PLD in porcine tracheal smooth muscle.

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“…Muscannic acetylcholine receptors (mAChR) are coupled to PI hydrolysis in a number of different tissues. In addition, they have been shown to stimulate PC hydrolysis in a variety of tissues (Corradetti et al, 1983;Doleial and TuCek, 1984;Brehm et al, 1985Brehm et al, , 1987Lindmar et al, 1986Lindmar et al, , 1988Martinson et al, 1989). Indirect evidence (Lindmar et al, 1986) and direct measurements showing parallel formation of PA and choline in stimulated tissues (Lindmar et al, 1988;Martinson et al, 1989) led to the hypothesis that mAChR stimulate PC hydrolysis by activating PLD.…”

mentioning

confidence: 99%

Stimulation of Phospholipase D Activity in Human Neuroblastoma (LA‐N‐2) Cells by Activation of Muscarinic Acetylcholine Receptors or by Phorbol Esters: Relationship to Phosphoinositide Turnover

Sandmann

Wurtman

1991

Journal of Neurochemistry

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We have investigated the coupling of muscarinic acetylcholine receptors (mAChR) to phospholipid hydrolysis in a human neuroblastoma cell line, LA-N-2, by measuring the formation of 3H-inositol phosphates (3H-IP) and of [3H]phosphatidylethanol ([3H]PEt) in cells prelabeled with [3H]inositol and [3H]oleic acid. The muscarinic agonist carbachol (CCh) stimulated the phospholipase C (PLC)-mediated formation of 3H-IP in a time- and dose-dependent manner (EC50 = 40-55 microM). In addition, in the presence of ethanol (170-300 mM), CCh elevated levels of [3H]PEt [which is regarded as a specific indicator of phospholipase D (PLD) activity] by three- to sixfold. The effect of CCh on PEt formation also was dose dependent (EC50 = 50 microM). Both effects of CCh were antagonized by atropine, indicating that they were mediated by mAChR. Incubation of LA-N-2 cells with the phorbol ester phorbol 12-myristate 13-acetate (PMA, 0.1 microM; 10 min) increased [3H]PEt levels by up to 10-fold. This effect was inhibited by the protein kinase C (PKC) inhibitor staurosporine (1 microM) or by pretreatment for 24 h with 0.1 microM PMA, by 74% and 65%, respectively. In contrast, the effect of CCh on PEt accumulation was attenuated by only 28% in the presence of staurosporine (1 microM). In summary, these results suggest that, in LA-N-2 neuroblastoma cells, mAChR are coupled both to phosphoinositide-specific PLC and to PLD. PKC is capable of stimulating PLD activity in these cells; however, it is not required for stimulation of the enzyme by mAChR activation.

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Muscarinic mobilization of choline in rat cerebral cortex does not involve alterations of blood-brain barrier

Cited by 15 publications

References 22 publications

Small Rises in Plasma Choline Reverse the Negative Arteriovenous Difference of Brain Choline

Small Rises in Plasma Choline Reverse the Negative Arteriovenous Difference of Brain Choline

Activation of Muscarinic Receptors in Porcine Airway Smooth Muscle Elicits a Transient Increase in Phospholipase D Activity

Stimulation of Phospholipase D Activity in Human Neuroblastoma (LA‐N‐2) Cells by Activation of Muscarinic Acetylcholine Receptors or by Phorbol Esters: Relationship to Phosphoinositide Turnover

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