The role of adenosine receptors and L-type calcium channels in the regulation of the mediator secretion in mouse motor synapses

Background Volatile anesthetics depress cardiac contractility, which involves inhibition of cardiac L-type calcium channels. To explore the role of voltage-dependent inactivation, the authors analyzed halothane effects on recombinant cardiac L-type calcium channels (alpha1Cbeta2a and alpha1Cbeta2aalpha2/delta1), which differ by the alpha2/delta1 subunit and consequently voltage-dependent inactivation. Methods HEK-293 cells were transiently cotransfected with complementary DNAs encoding alpha1C tagged with green fluorescent protein and beta2a, with and without alpha2/delta1. Halothane effects on macroscopic barium currents were recorded using patch clamp methodology from cells expressing alpha1Cbeta2a and alpha1Cbeta2aalpha2/delta1 as identified by fluorescence microscopy. Results Halothane inhibited peak current (I(peak)) and enhanced apparent inactivation (reported by end pulse current amplitude of 300-ms depolarizations [I300]) in a concentration-dependent manner in both channel types. alpha2/delta1 coexpression shifted relations leftward as reported by the 50% inhibitory concentration of I(peak) and I300/I(peak)for alpha1Cbeta2a (1.8 and 14.5 mm, respectively) and alpha1Cbeta2aalpha2/delta1 (0.74 and 1.36 mm, respectively). Halothane reduced transmembrane charge transfer primarily through I(peak) depression and not by enhancement of macroscopic inactivation for both channels. Conclusions The results indicate that phenotypic features arising from alpha2/delta1 coexpression play a key role in halothane inhibition of cardiac L-type calcium channels. These features included marked effects on I(peak) inhibition, which is the principal determinant of charge transfer reductions. I(peak) depression arises primarily from transitions to nonactivatable states at resting membrane potentials. The findings point to the importance of halothane interactions with states present at resting membrane potential and discount the role of inactivation apparent in current time courses in determining transmembrane charge transfer.

Download Full-text

Benzodiazepine-induced hippocampal CA1 neuron ??-amino-3-hydroxy-5-methylisoxasole-4-propionic acid (AMPA) receptor plasticity linked to severity of withdrawal anxiety: differential role of voltage-gated calcium channels and N-methyl-D-aspartic acid receptors

Behavioural Pharmacology ◽

10.1097/fbp.0b013e3282d28f2b ◽

2007 ◽

Vol 18 (5-6) ◽

pp. 447-460 ◽

Cited By ~ 25

Author(s):

Kun Xiang ◽

Elizabeth I. Tietz

Keyword(s):

Calcium Channels ◽

Aspartic Acid ◽

Propionic Acid ◽

Ampa Receptor ◽

Voltage Gated ◽

Voltage Gated Calcium Channels ◽

Hippocampal Ca1 ◽

Receptor Plasticity

Download Full-text

Role of ?-conotoxin-sensitive calcium channels in inositolphosphate production and noradrenaline release due to potassium depolarization or stimulation with carbachol

Naunyn-Schmiedeberg s Archives of Pharmacology ◽

10.1007/bf00169731 ◽

1990 ◽

Vol 341 (3) ◽

Cited By ~ 11

Author(s):

Fred Hofmann ◽

Ernst Habermann

Keyword(s):

Calcium Channels ◽

Noradrenaline Release ◽

Potassium Depolarization

Download Full-text

Role of the extracellular cAMP-adenosine pathway in renal physiology

AJP Renal Physiology ◽

10.1152/ajprenal.2001.281.4.f597 ◽

2001 ◽

Vol 281 (4) ◽

pp. F597-F612 ◽

Cited By ~ 69

Author(s):

Edwin K. Jackson ◽

Raghvendra K. Dubey

Keyword(s):

Adenosine Receptors ◽

Epithelial Transport ◽

Receptor Activation ◽

Hormonal Control ◽

Renal Physiology ◽

Tight Coupling ◽

Extracellular Adenosine ◽

Mediated Effects ◽

Extracellular Camp

Adenosine exerts physiologically significant receptor-mediated effects on renal function. For example, adenosine participates in the regulation of preglomerular and postglomerular vascular resistances, glomerular filtration rate, renin release, epithelial transport, intrarenal inflammation, and growth of mesangial and vascular smooth muscle cells. It is important, therefore, to understand the mechanisms that generate extracellular adenosine within the kidney. In addition to three “classic” pathways of adenosine biosynthesis, contemporary studies are revealing a novel mechanism for renal adenosine production termed the “extracellular cAMP-adenosine pathway.” The extracellular cAMP-adenosine pathway is defined as the egress of cAMP from cells during activation of adenylyl cyclase, followed by the extracellular conversion of cAMP to adenosine by the serial actions of ecto-phosphodiesterase and ecto-5′-nucleotidase. This mechanism of extracellular adenosine production may provide hormonal control of adenosine levels in the cell-surface biophase in which adenosine receptors reside. Tight coupling of the site of adenosine production to the site of adenosine receptors would permit a low-capacity mechanism of adenosine biosynthesis to have a large impact on adenosine receptor activation. The purposes of this review are to summarize the physiological roles of adenosine in the kidney; to describe the classic pathways of renal adenosine biosynthesis; to review the evidence for the existence of the extracellular cAMP-adenosine pathway; and to describe possible physiological roles of the extracellular cAMP-adenosine pathway, with particular emphasis on the kidney.

Download Full-text

Role of Adenosine Receptors in Rare Neurodegenerative Diseases with Motor Symptoms

Current Protein and Peptide Science ◽

10.2174/1389203722666210910110126 ◽

2021 ◽

Vol 22 ◽

Author(s):

Vicent Beltran-Beltran ◽

Noelia Benetó ◽

Tamara Lapeña-Luzón ◽

Laura R. Rodríguez ◽

Federico V. Pallardó ◽

...

Keyword(s):

Neurodegenerative Diseases ◽

Adenosine Receptors ◽

Spinocerebellar Ataxia Type ◽

European Medicines Agency ◽

Receptor Subtypes ◽

Motor Symptoms ◽

Spinocerebellar Ataxia Type 3 ◽

Adenosine 2A Receptor ◽

Type 3

: The approval of istradefylline, an adenosine 2A receptor (A2AR) antagonist, as an add-on treatment in adult patients with Parkinson’s disease by the Food and Drug Administration (FDA) and European Medicines Agency (EMA), is the latest proof of the importance of the adenosinergic system in the nervous system. Adenosine is an endogenous purine nucleoside with a role as a modulator of both neurotransmission and the inflammatory response. As such, the expression pattern of the 4 adenosine receptors (A1R, A2AR, A2BR and A3R) and the extracellular adenosine levels have attracted great interest in the pathogenesis and possible treatment of rare neurodegenerative diseases with motor symptoms. These include Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), restless legs syndrome (RLS) and Machado-Joseph disease (MJD, also known as spinocerebellar ataxia type 3, SCA3). In this review, we shall focus on the role of the different adenosine receptor subtypes in the development and possible treatment of the aforementioned rare neurodegenerative diseases with motor symptoms using the currently available data. The last section discusses the possibility of a role for the adenosine receptors in the treatment of other rare diseases based on the available molecular pathology knowledge.

Download Full-text