Chemical and Pharmacological Screening of Rhinella icterica (Spix 1824) Toad Parotoid Secretion in Avian Preparations

The biological activity of Rhinella icterica parotoid secretion (RIPS) and some of its chromatographic fractions (RI18, RI19, RI23, and RI24) was evaluated in the current study. Mass spectrometry of these fractions indicated the presence of sarmentogenin, argentinogenin, (5β,12β)-12,14-dihydroxy-11-oxobufa-3,20,22-trienolide, marinobufagin, bufogenin B, 11α,19-dihydroxy-telocinobufagin, bufotalin, monohydroxylbufotalin, 19-oxo-cinobufagin, 3α,12β,25,26-tetrahydroxy-7-oxo-5β-cholestane-26-O-sulfate, and cinobufagin-3-hemisuberate that were identified as alkaloid and steroid compounds, in addition to marinoic acid and N-methyl-5-hydroxy-tryptamine. In chick brain slices, all fractions caused a slight decrease in cell viability, as also seen with the highest concentration of RIPS tested. In chick biventer cervicis neuromuscular preparations, RIPS and all four fractions significantly inhibited junctional acetylcholinesterase (AChE) activity. In this preparation, only fraction RI23 completely mimicked the pharmacological profile of RIPS, which included a transient facilitation in the amplitude of muscle twitches followed by progressive and complete neuromuscular blockade. Mass spectrometric analysis showed that RI23 consisted predominantly of bufogenins, a class of steroidal compounds known for their cardiotonic activity mediated by a digoxin- or ouabain-like action and the blockade of voltage-dependent L-type calcium channels. These findings indicate that the pharmacological activities of RI23 (and RIPS) are probably mediated by: (1) inhibition of AChE activity that increases the junctional content of Ach; (2) inhibition of neuronal Na+/K+-ATPase, leading to facilitation followed by neuromuscular blockade; and (3) blockade of voltage-dependent Ca2+ channels, leading to stabilization of the motor endplate membrane.

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An Overview on Phytochemical and Pharmacological Profile of Morus alba Linn.

Current Bioactive Compounds ◽

10.2174/1573407216666201228114004 ◽

2020 ◽

Vol 16 ◽

Author(s):

Arpita Paul ◽

Monami Rajiung ◽

Kamaruz Zaman ◽

Sushil Kumar Chaudhary ◽

Hans Raj Bhat ◽

...

Keyword(s):

Traditional Medicine ◽

Morus Alba ◽

Biologically Active ◽

Pharmacological Profile ◽

Pharmacological Activities ◽

Significant Information ◽

The Past ◽

Comprehensive Information ◽

The Family ◽

White Mulberry

Background: Morus alba Linn. commonly known as white mulberry, belongs to the family Moraceae, is a promising traditional medicine. In Asia, besides its use in the preparation of delicacies, every part of this plant is utilized in traditional medicine. Over the past decade, studies related to identification and isolation of biologically active compounds, with flavonoids as the major class of phytoconstituents, from this plant has been reported. These phytoconstituents are not only found to be beneficial for the maintenance of general health but also are associated with a range of potential pharmacological activities such as antioxidant, anti-inflammatory, anti-diabetic, anticancer, hepatoprotective, cardioprotective, neuroprotective to name a few. Objective: This review aims to provide upgraded and comprehensive information regarding the phytochemical, ethnomedicinal use and pharmacological profile of the plant Morus alba Linn. Method: The significant information has been collected through various database viz. PubMed, Scopus, Web of Science, Science Direct based on the recent findings, using different terms of Morus alba. Results: The outcome of the study suggests that Morus alba is a multifunctional plant numerous phytochemicals, and possess a range of pharmacological activities. Conclusion: The data assembled on Morus alba will be beneficial to trigger research in various fields of pharmaceutical and allied science to explore the medicinal importance of this unique plant.

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Role of Ca2+ and Na+ on luteinizing hormone release from the calf pituitary

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1988.255.4.e469 ◽

1988 ◽

Vol 255 (4) ◽

pp. E469-E474

Author(s):

J. P. Kile ◽

M. S. Amoss

Keyword(s):

Luteinizing Hormone ◽

Ionophore A23187 ◽

Channel Blockers ◽

Hormone Release ◽

Primary Cells ◽

Rat Pituitary ◽

Voltage Dependent ◽

Lh Release ◽

Ca2 Channels

It has been proposed that gonadotropin-releasing hormone (GnRH) stimulates Ca2+ entry by activation of voltage-independent, receptor-mediated Ca2+ channels in the rat gonadotroph. Little work has been done on the role of calcium in GnRH-induced luteinizing hormone (LH) release in species other than the rat. Therefore, this study was done to compare the effects of agents that alter Ca2+ or Na+ entry on LH release from calf anterior pituitary primary cells in culture. GnRH (100 ng/ml), Ca2+ ionophore A23187 (2.5 microM), and the depolarizing agent ouabain (0.1-10 microM) all produced significant increases (P less than 0.05) in LH release; these effects were significantly reduced when the cells were preincubated with the organic Ca2+ channel blockers nifedipine (1-10 microM) and verapamil (1-10 microM) and with Co2+ (0.01-1 mM). The effect of ouabain was inhibited by tetrodotoxin (TTX; 1-10 nM) as well as by nifedipine at 0.1-10 microM. In contrast to its effect on rat pituitary LH release, TTX significantly inhibited GnRH-stimulated LH release at 1-100 nM. These results suggest that GnRH-induced LH release may employ Ca2+ as a second messenger in bovine gonadotrophs and support recent speculation that GnRH-induced Ca2+ mobilization may in part be voltage dependent.

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Intracellular Na+inhibits voltage-dependent N-type Ca2+channels by a G protein βγ subunit-dependent mechanism

The Journal of Physiology ◽

10.1113/jphysiol.2003.056168 ◽

2004 ◽

Vol 556 (1) ◽

pp. 121-134 ◽

Cited By ~ 20

Author(s):

Yakov Blumenstein ◽

Olexandr P. Maximyuk ◽

Natalia Lozovaya ◽

Natalia M. Yatsenko ◽

Nataly Kanevsky ◽

...

Keyword(s):

G Protein ◽

Voltage Dependent ◽

Ca2 Channels ◽

Dependent Mechanism

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Wogonin preferentially kills malignant lymphocytes and suppresses T-cell tumor growth by inducing PLCγ1- and Ca2+-dependent apoptosis

Blood ◽

10.1182/blood-2007-06-096198 ◽

2008 ◽

Vol 111 (4) ◽

pp. 2354-2363 ◽

Cited By ~ 102

Author(s):

Sven Baumann ◽

Stefanie C. Fas ◽

Marco Giaisi ◽

Wolfgang W. Müller ◽

Anette Merling ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Therapeutic Potential ◽

Human T Cell ◽

Voltage Dependent ◽

Ca2 Channels ◽

Malignant T Cells

Herbs have successfully been used in traditional Chinese medicine for centuries. However, their curative mechanisms remain largely unknown. In this study, we show that Wogonin, derived from the traditional Chinese medicine Huang-Qin (Scutellaria baicalensis Georgi), induces apoptosis in malignant T cells in vitro and suppresses growth of human T-cell leukemia xenografts in vivo. Importantly, Wogonin shows almost no toxicity on T lymphocytes from healthy donors. Wogonin induces prolonged activation of PLCγ1 via H2O2 signaling in malignant T cells, which leads to sustained elevation of cytosolic Ca2+ in malignant but not normal T cells. Subsequently, a Ca2+ overload leads to disruption of the mitochondrial membrane. The selective effect of Wogonin is due to its differential regulation of the redox status of malignant versus normal T cells. In addition, we show that the L-type voltage-dependent Ca2+ channels are involved in the intracellular Ca2+ mobilization in T cells. Furthermore, we show that malignant T cells possess elevated amounts of voltage-dependent Ca2+ channels compared with normal T cells, which further enhance the cytotoxicity of Wogonin for malignant T cells. Taken together, our data show a therapeutic potential of Wogonin for the treatment of hematologic malignancies.

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Gonadotropin-Releasing Hormone Inhibits Ether-à-Go-Go-Related Gene K+ Currents in Mouse Gonadotropes

Endocrinology ◽

10.1210/en.2009-0718 ◽

2010 ◽

Vol 151 (3) ◽

pp. 1079-1088 ◽

Cited By ~ 5

Author(s):

Wiebke Hirdes ◽

Crenguta Dinu ◽

Christiane K. Bauer ◽

Ulrich Boehm ◽

Jürgen R. Schwarz

Keyword(s):

Resting Potential ◽

Related Gene ◽

Activation Curve ◽

Signal Cascade ◽

Primary Mouse ◽

Voltage Dependent ◽

K Current ◽

Unknown Signal ◽

Ca2 Channels ◽

K Currents

Secretion of LH from gonadotropes is initiated by a GnRH-induced increase in intracellular Ca2+ concentration ([Ca2+]i). This increase in [Ca2+]i is the result of Ca2+ release from intracellular stores and Ca2+ influx through voltage-dependent Ca2+ channels. Here we describe an ether-à-go-go-related gene (erg) K+ current in primary mouse gonadotropes and its possible function in the control of Ca2+ influx. To detect gonadotropes, we used a knock-in mouse strain, in which GnRH receptor-expressing cells are fluorescently labeled. Erg K+ currents were recorded in 80–90% of gonadotropes. Blockage of erg currents by E-4031 depolarized the resting potential by 5–8 mV and led to an increase in [Ca2+]i, which was abolished by nifedipine. GnRH inhibited erg currents by a reduction of the maximal erg current and in some cells additionally by a shift of the activation curve to more positive potentials. In conclusion, the erg current contributes to the maintenance of the resting potential in gonadotropes, thereby securing a low [Ca2+]i by restricting Ca2+ influx. In addition, the erg channels are modulated by GnRH by an as-yet unknown signal cascade.

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A Complex of RIM2alpha and RIM-Binding Protein 2 Stabilizes Slow Voltage-Dependent Inactivation of Cochlear Inner Hair Cell Cav1.3 L-Type Ca2+ Channels

Biophysical Journal ◽

10.1016/j.bpj.2017.11.3443 ◽

2018 ◽

Vol 114 (3) ◽

pp. 637a-638a

Author(s):

Nadine J. Ortner ◽

Alexandra Pinggera ◽

Anita Siller ◽

Nadja Hofer ◽

Niels Brandt ◽

...

Keyword(s):

Hair Cell ◽

Binding Protein ◽

Inner Hair Cell ◽

Dependent Inactivation ◽

Voltage Dependent ◽

Ca2 Channels

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NO-mediated MaxiKCa channel activation produces relaxation of guinea pig aorta independently of voltage-dependent L-type Ca2+ channels

General Pharmacology The Vascular System ◽

10.1016/s0306-3623(00)00056-2 ◽

2000 ◽

Vol 34 (3) ◽

pp. 159-165 ◽

Cited By ~ 9

Author(s):

Yoshio Tanaka ◽

Tomomi Igarashi ◽

Hiroki Kaneko ◽

Fumiko Yamaki ◽

Yumi Mochizuki ◽

...

Keyword(s):

Guinea Pig ◽

Channel Activation ◽

Voltage Dependent ◽

Ca2 Channels

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Voltage-gated transient currents in bovine adrenal fasciculata cells. I. T-type Ca2+ current.

The Journal of General Physiology ◽

10.1085/jgp.102.2.217 ◽

1993 ◽

Vol 102 (2) ◽

pp. 217-237 ◽

Cited By ~ 30

Author(s):

B Mlinar ◽

B A Biagi ◽

J J Enyeart

Keyword(s):

Time Constant ◽

Low Voltage ◽

Zona Fasciculata ◽

Patch Clamp Technique ◽

Time Constants ◽

Voltage Gated ◽

Wide Range ◽

Boltzmann Function ◽

Voltage Dependent ◽

Ca2 Channels

The whole cell version of the patch clamp technique was used to identify and characterize voltage-gated Ca2+ channels in enzymatically dissociated bovine adrenal zona fasciculata (AZF) cells. The great majority of cells (84 of 86) expressed only low voltage-activated, rapidly inactivating Ca2+ current with properties of T-type Ca2+ current described in other cells. Voltage-dependent activation of this current was fit by a Boltzmann function raised to an integer power of 4 with a midpoint at -17 mV. Independent estimates of the single channel gating charge obtained from the activation curve and using the "limiting logarithmic potential sensitivity" were 8.1 and 6.8 elementary charges, respectively. Inactivation was a steep function of voltage with a v1/2 of -49.9 mV and a slope factor K of 3.73 mV. The expression of a single Ca2+ channel subtype by AZF cells allowed the voltage-dependent gating and kinetic properties of T current to be studied over a wide range of potentials. Analysis of the gating kinetics of this Ca2+ current indicate that T channel activation, inactivation, deactivation (closing), and reactivation (recovery from inactivation) each include voltage-independent transitions that become rate limiting at extreme voltages. Ca2+ current activated with voltage-dependent sigmoidal kinetics that were described by an m4 model. The activation time constant varied exponentially at test potentials between -30 and +10 mV, approaching a voltage-independent minimum of 1.6 ms. The inactivation time constant (tau i) also decreased exponentially to a minimum of 18.3 ms at potentials positive to 0 mV. T channel closing (deactivation) was faster at more negative voltages; the deactivation time constant (tau d) decreased from 8.14 +/- 0.7 to 0.48 +/- 0.1 ms at potentials between -40 and -150 mV. T channels inactivated by depolarization returned to the closed state along pathways that included two voltage-dependent time constants. tau rec-s ranged from 8.11 to 4.80 s when the recovery potential was varied from -50 to -90 mV, while tau rec-f decreased from 1.01 to 0.372 s. At potentials negative to -70 mV, both time constants approached minimum values. The low voltage-activated Ca2+ current in AZF cells was blocked by the T channel selective antagonist Ni2+ with an IC50 of 20 microM. At similar concentrations, Ni2+ also blocked cortisol secretion stimulated by adrenocorticotropic hormone. Our results indicate that bovine AZF cells are distinctive among secretory cells in expressing primarily or exclusively T-type Ca2+ channels.(ABSTRACT TRUNCATED AT 400 WORDS)

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