Effects of 2,5-di(tert-butyl)-1,4-Hydroquinone, an Endoplasmic Reticulum Ca2+-ATPase Inhibitor, on Agonist-Stimulated Phasic Myometrial Contractions

Phillippe, Mark; Kim, J.; Freij, Maysoun; Saunders, Trevania

doi:10.1006/bbrc.1995.1269

Cited by 3 publications

(2 citation statements)

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“…Interestingly, we observed that tBHQ did not inhibit the neuronal L-type ICa, whereas it inhibited non-neuronal Ltype ICa (i.e., in neuroendocrine cells; Nelson et al, 1994), probably in smooth muscle cells (Philippe et al, 1995) and L-type ICa in differentiated NG108-15 cells (present study). Moreover, the poor sensitivity of the neuronal ␣1C subunit to tBHQ in the oocyte expression system appears to be consistent with the inefficacy of this drug in the various neuronal preparations tested.…”

Section: Sarco-endoplasmic Atpase Blocker Inhibits Ca 2؉ Currentscontrasting

confidence: 43%

Sarco-Endoplasmic ATPase Blocker 2,5-Di(tert-butyl)-1,4-benzohydroquinone Inhibits N-, P-, and Q- but Not T-, L-, or R-Type Calcium Currents in Central and Peripheral Neurons

Scamps¹,

Vigues²,

Restituito³

et al. 2000

Mol Pharmacol

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The effects of 2,5-di(tert-butyl)-1,4-benzohydroquinone (tBHQ), a synthetic phenolic antioxidant and a blocker of the sarcoendoplasmic ATPase, were evaluated on low and high voltageactivated Ca 2ϩ currents (ICas) with rodent dorsal root ganglion, hippocampal, and motor neurons. In all cell types tested, tBHQ (IC 50 ϭ 35 M) blocked ICa at concentrations used to inhibit sarco-endoplasmic ATPase. This effect was specific to tBHQ because the other sarco-endoplasmic reticulum calcium ATPase pump inhibitors (thapsigargin and cyclopiazonic acid) had no effect. Selective blockade of the N-type current with -conotoxin GVIA and of P-(motoneuron) or Q-type currents (hippocampal neuron) with -agatoxin IVA indicated that tBHQ inhibited N, P, and Q types of ICa. tBHQ had no effect on nitrendipine-sensitive (L-type) and residual drug-resistant (Rtype) ICa, nor on the low voltage-activated T-type ICa. Contrary to neuronal cells, the L-type ICa was inhibited by tBHQ in a differentiated mouse neuroblastoma and rat glioma hybrid cell line. Injection of cDNAs encoding the ␣1A, ␣1B, ␣1C, and ␣1E subunits into oocytes showed that tBHQ blocked ICas at the level of the pore-forming protein. This effect of tBHQ on ICa should be considered when interpreting results obtained with tBHQ used on neuronal preparations. It also may be useful for developing new strategies for the generation of more potent intracellular calcium transient inhibitors.Plasmalemmal voltage-gated calcium channels (VGCCs) initiate intracellular calcium transients and control many aspects of neuronal processes, including the generation of calcium-dependent action potentials, neurotransmitter release, regulation of neuronal death, synapse formation and elimination, phenotypic differentiation, and gene expression (Ghosh and Greenberg, 1995;Gu and Spitzer, 1997). These channels are activated by membrane depolarization, leading to a transmembrane calcium influx and a transient increase in cytoplasmic free calcium concentration. It has become clear, however, that these voltage-dependent calcium transients also are generated by mechanisms involving the release of calcium from intracellular stores in the sarco-endoplasmic reticulum. In neurons, at least two types of calcium stores have been identified in the sarco-endoplasmic reticulum, based on calcium-release channels: caffeine-ryanodinesensitive and inositol-1,3,4-triphosphate-sensitive calcium channels. The relationships among voltage-activated calcium influx, release of calcium from cytoplasmic stores, and intracellular calcium transients are complex and are only just beginning to be understood.Five VGCC subtypes (T, L, N, P/Q, and R) were initially defined according to electrophysiological and pharmacological characteristics (Birnbaumer et al., 1994) and, more recently, these definitions have been extended to take into account amino acid sequences (Perez-Reyes and Schneider, 1994;Perez-Reyes et al., 1998). Similarly, at least three intracellular calcium channel subtypes have been characterized at the molecular l...

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Section: Sarco-endoplasmic Atpase Blocker Inhibits Ca 2؉ Currentscontrasting

confidence: 43%

Sarco-Endoplasmic ATPase Blocker 2,5-Di(tert-butyl)-1,4-benzohydroquinone Inhibits N-, P-, and Q- but Not T-, L-, or R-Type Calcium Currents in Central and Peripheral Neurons

Scamps¹,

Vigues²,

Restituito³

et al. 2000

Mol Pharmacol

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“…The only other reports of the contribution of SERCA to the regulation of myometrial contractility have been performed in muscle from nonpregnant [9,25,26] and pregnant rats [9]. It is interesting that the CPA response observed in spontaneously contracting human NL tissue resembled the responses reported in nonpregnant rat myometrium, and that CPA-induced changes in human AL myometrium contractions resembled those of term, NL pregnant rat [9].…”

Section: Serca Inhibition In Spontaneously Contracting Human Myometriummentioning

confidence: 66%

Calcium Homeostatic Pathways Change with Gestation in Human Myometrium1

Tribe

Moriarty

Poston

2000

Biology of Reproduction

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A rise in intracellular calcium is the primary trigger for contractile activity in pregnant human myometrium. It is hypothesized that key proteins involved in myometrial calcium homeostasis are gestationally regulated and play an important role in the preparation for labor. The aims of the study were to investigate the role of sarcoplasmic reticulum Ca ATPases (SERCAs) in regulating spontaneous contractile activity in myometrium, and to determine the expression of SERCA isoforms 2a and 2b, and the plasma membrane Ca ATPase (PMCA), at term and during labor. Western blot analysis demonstrated that the expression of SERCA 2a and 2b significantly increased in myometrium of women in labor compared with those not in labor. The augmentation of contractile activity in laboring myometrium in the presence of a SERCA 2 inhibitor, cyclopiazonic acid (CPA), demonstrated the functional significance of this observation. It is interesting that the application of CPA in the presence of a calcium-activated potassium channel inhibitor to term nonlabor myometrium mimicked the response of myometrium from women in active labor to CPA alone. We conclude that the activity of SERCA isoforms becomes increasingly important in the maintenance of regular contractile activity during labor and may compensate for the functional loss of other calcium control pathways at term.

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(+)cis-Dioxolane Stimulation of Cytosolic Calcium Oscillations and Phasic Contractions of Myometrial Smooth Muscle

Phillippe

Basa

1997

Biochemical and Biophysical Research Communications

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Effects of 2,5-di(tert-butyl)-1,4-Hydroquinone, an Endoplasmic Reticulum Ca2+-ATPase Inhibitor, on Agonist-Stimulated Phasic Myometrial Contractions

Cited by 3 publications

References 0 publications

Sarco-Endoplasmic ATPase Blocker 2,5-Di(tert-butyl)-1,4-benzohydroquinone Inhibits N-, P-, and Q- but Not T-, L-, or R-Type Calcium Currents in Central and Peripheral Neurons

Sarco-Endoplasmic ATPase Blocker 2,5-Di(tert-butyl)-1,4-benzohydroquinone Inhibits N-, P-, and Q- but Not T-, L-, or R-Type Calcium Currents in Central and Peripheral Neurons

Calcium Homeostatic Pathways Change with Gestation in Human Myometrium1

(+)cis-Dioxolane Stimulation of Cytosolic Calcium Oscillations and Phasic Contractions of Myometrial Smooth Muscle

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