ATP modulation of calcium channels in chromaffin cells.

Gandı́a, Luis; Garcı́a, Antonio G.; Morad, Martin

doi:10.1113/jphysiol.1993.sp019847

Cited by 105 publications

(103 citation statements)

References 46 publications

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“…The same Hill coefficient was obtained for the inhibition of Ic. of chromaffin cells by ATP (Gandia et al, 1993), while for ICa inhibition in ferret ventricular cells a 1:1 binding of ligand to receptor was suggested (Qu et al, 1993b). Suramin and cibacron blue were competitive antagonists, which suggests that they act at the ATP binding site.…”

Section: Discussionmentioning

confidence: 99%

Pharmacological profile of the ATP‐mediated increase in L‐type calcium current amplitude and activation of a non‐specific cationic current in rat ventricular cells

Scamps

Vassort

1994

British J Pharmacology

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1 The pharmacological profile of the ATP-induced increase in Ica amplitude and of ATP activation of a non-specific cationic current, IATp, was investigated in rat ventricular cells.2 The EC50 values for Ic, increase and IATp activation were 0.36 pM and 0.76 FtM respectively. Suramin (1O tM) and cibacron blue (1 gM) competitively antagonized both effects of ATP. 3 The rank order of efficacy and potency of ATP analogues in increasing IC, amplitude was 2-methylthio-ATP ftATPtATPyS. The derivatives j-methylene-ATP, P,'y-methylene-ATP and 0,yimido-ATP up to 500 LM had no significant effects. 4 The rank order of efficacy of ATP analogues in activating a non-specific cationic current, IATp, was 2-methylthio-ATP >ATP >>ATPyS. The rank order of potency was 2-methylthio-ATPtATP. The EC" of ATPyS could not be determined owing to its very low efficacy. 5 The ATP analogues ,-methylene-ATP, ,'y-methylene-ATP and P,y-imido-ATP at 500 AM did not activate IATP but acted as antagonists of activation of IATP by ATP.6 The results suggest that the increase in Ic. amplitude induced by external ATP is due to activation of P2y-purinoceptors. 7 The mechanism of IATP activation remains to be determined before the receptor subtype involved can be deduced.

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Section: Discussionmentioning

confidence: 99%

Pharmacological profile of the ATP‐mediated increase in L‐type calcium current amplitude and activation of a non‐specific cationic current in rat ventricular cells

Scamps

Vassort

1994

British J Pharmacology

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“…3, cells were stimulated with a high concentration of the nicotinic agonist DMPP for a long period (5 min), whereby most nicotinic receptors should be desensitized and the secreted ATP is most likely to act on purinergic autoreceptors (39). To avoid these effects, rapid perfusion was used and VNUT-KD was seen to mainly affect only the first two to three secretory responses, the later secretory peaks remaining unaffected.…”

Section: Discussionmentioning

confidence: 99%

ATP: The crucial component of secretory vesicles

Estévez-Herrera

Domínguez

Pardo

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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The colligative properties of ATP and catecholamines demonstrated in vitro are thought to be responsible for the extraordinary accumulation of solutes inside chromaffin cell secretory vesicles, although this has yet to be demonstrated in living cells. Because functional cells cannot be deprived of ATP, we have knocked down the expression of the vesicular nucleotide carrier, the VNUT, to show that a reduction in vesicular ATP is accompanied by a drastic fall in the quantal release of catecholamines. This phenomenon is particularly evident in newly synthesized vesicles, which we show are the first to be released. Surprisingly, we find that inhibiting VNUT expression also reduces the frequency of exocytosis, whereas the overexpression of VNUT drastically increases the quantal size of exocytotic events. To our knowledge, our data provide the first demonstration that ATP, in addition to serving as an energy source and purinergic transmitter, is an essential element in the concentration of catecholamines in secretory vesicles. In this way, cells can use ATP to accumulate neurotransmitters and other secreted substances at high concentrations, supporting quantal transmission.exocytosis | purines | quantum size | secretory vesicles | VNUT V irtually most, and possibly all, types of secretory vesicles found in cells contain ATP, which often accumulates at high concentrations and, commonly, in conjunction with different types of neurotransmitters. However, the reason for this widespread distribution of ATP remains a mystery. Although ATP is present in all animal species, including primitive life forms like Giardia lamblia that lack Golgi complexes and mitochondria, the detection of ATP in the secretory vesicles of sympathetic neurons was considered to be the first example of cotransmission (1). However, given the ubiquitous accumulation of ATP in secretory vesicles, it might instead be considered that it is the other neurotransmitters that coincide with ATP, rather than the other way around (2). Indeed, perhaps ATP should be considered as the first molecule used as a transmitter in primitive forms of life.Astonishingly high concentrations of releasable species are stored inside secretory vesicles, far exceeding those in the cytosol (3, 4). For example, the catecholamine content of adrenal secretory granules (SGs), a type of large dense core secretory vesicles also known as chromaffin granules, was 0.8-1 M when measured directly in adrenal chromaffin cells using patch amperometry (5, 6). In addition, SGs from chromaffin cells contain ATP at ∼150 mM (7), calcium ∼40 mM (8), about 2 mM of granins, ascorbate, peptides, and other nucleotides, all in an acidic pH ∼5.5 environment.ATP possesses intrinsic chemical characteristics that make it relevant to the accumulation of soluble substances in secretory vesicles. The formation of weak complexes between monoamines and ATP, the two main soluble compounds in chromaffin granules, has been demonstrated in vitro by NMR (9), ultracentrifugation (10), infrared spectroscopy, and calorime...

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“…The chamber was perfused continuously, at room temperature, with Krebs'-HEPES. Solutions containing ACh and/or catestatin were changed using a multibarreled concentration-clamp device (Gandía et al, 1993). Only one experimental protocol was run on each single coverslip.…”

Section: Methodsmentioning

confidence: 99%

Modulatory Mechanism of the Endogenous Peptide Catestatin on Neuronal Nicotinic Acetylcholine Receptors and Exocytosis

et al. 2002

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The catestatin fragment of chromogranin A is the first known endogenous compound able to inhibit catecholamine release elicited by the activation of neuronal nicotinic acetylcholine receptors (nAChRs) of different animal species and catecholaminergic cell types. However, how catestatin regulates the receptor activity, which subunit combination of the heteropentameric forms of receptor is better blocked by the peptide, or how it affects the different stages of the exocytotic process have not yet been evaluated. To address these questions, we have assayed the effects of catestatin: (first) on the inward currents elicited by ACh (I ACh ) in voltage-clamped oocytes expressing different combinations of nAChR subunits; and (second) on the cytosolic Ca 2ϩ concentration, [Ca 2ϩ ] c , and quantal release of catecholamines simultaneously monitored in single adrenal chromaffin cells stimulated with ACh. Catestatin potently blocks all the subtypes of nAChRs studied. Furthermore, it inhibits the ␣ 3 ␤ 4 current in a reversible, noncompetitive, voltage-, and use-dependent manner, a behavior compatible with open-channel blockade. In fura-2-loaded single chromaffin cells, the peptide reduced the [Ca 2ϩ ] c signal and the total release of catecholamines elicited by ACh; however, catestatin did not modify the kinetics or the last step of the exocytotic process. Our results suggest that catestatin might play an autocrine regulatory role in neuroendocrine secretion through its interaction with different native nAChR subtypes; the extent of receptor blockade by the peptide could be acutely regulated by the intensity and duration of the presynaptic stimulus.

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ATP modulation of calcium channels in chromaffin cells.

Cited by 105 publications

References 46 publications

Pharmacological profile of the ATP‐mediated increase in L‐type calcium current amplitude and activation of a non‐specific cationic current in rat ventricular cells

Pharmacological profile of the ATP‐mediated increase in L‐type calcium current amplitude and activation of a non‐specific cationic current in rat ventricular cells

ATP: The crucial component of secretory vesicles

Modulatory Mechanism of the Endogenous Peptide Catestatin on Neuronal Nicotinic Acetylcholine Receptors and Exocytosis

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