Dual effects of theophylline on spontaneous transmitter release from frog motor nerve terminals

Barry, SR

doi:10.1523/jneurosci.08-12-04427.1988

Cited by 9 publications

(11 citation statements)

References 23 publications

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“…Firstly, selective A 2A or A 3 agonists and selective adenosine receptor antagonists were not examined in this study. Secondly, theophylline, used at high concentration (100 μM), is also a potent inhibitor of phosphodiesterases (Barry, 1988), and phosphodiesterase inhibition has been shown to increase IL-10 production (Mascali et al, 1996), thereby potentially masking its adenosine receptor antagonistic property. Thirdly, the adenosine uptake blocker dipyridamole was also incapable of preventing the stimulatory effect of adenosine on IL-10 production, secluding an intracellular, receptor-independent effect of adenosine.…”

Section: Adenosine Facilitates Il-10 Release By Monocytes and Macrophmentioning

confidence: 99%

Shaping of monocyte and macrophage function by adenosine receptors

Haskó

Pacher

Deitch

et al. 2007

Pharmacology & Therapeutics

194

154

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Adenosine is an endogenous purine nucleoside that, following its release into the extracellular space, binds to specific adenosine receptors expressed on the cell surface. Adenosine appears in the extracellular space under metabolically stressful conditions, which are associated with ischemia, inflammation, and cell damage. There are 4 types of adenosine receptors (A 1 , A 2A , A 2B and A 3 ) and all adenosine receptors are members of the G protein-coupled family of receptors. Adenosine receptors are expressed on monocytes and macrophages and through these receptors adenosine modulates monocyte and macrophage function. Since monocytes and macrophages are activated by the same danger signals that cause accumulation of extracellular adenosine, adenosine receptors expressed on macrophages represent a sensor system that provide monocytes and macrophages with information about the stressful environment. Adenosine receptors, thus, allow monocytes and macrophages to fine-tune their responses to stressful stimuli. Here, we review the consequences of adenosine receptor activation on monocyte/macrophage function. We will detail the effect of stimulating the various adenosine receptor subtypes on macrophage differentiation/proliferation, phagocytosis, and tissue factor (TF) expression. We will also summarize our knowledge of how adenosine impacts the production of extracellular mediators secreted by monocytes and macrophages in response to toll-like receptor (TLR) ligands and other inflammatory stimuli. Specifically, we will delineate how adenosine affects the production of superoxide, nitric oxide (NO), tumor necrosis factor-α, interleukin (IL)-12, IL-10, and vascular endothelial growth factor (VEGF). A deeper insight into the regulation of monocyte and macrophage function by adenosine receptors should assist in developing new therapies for inflammatory diseases.

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Section: Adenosine Facilitates Il-10 Release By Monocytes and Macrophmentioning

confidence: 99%

Shaping of monocyte and macrophage function by adenosine receptors

Haskó

Pacher

Deitch

et al. 2007

Pharmacology & Therapeutics

194

154

View full text Add to dashboard Cite

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“…(Ribeiro & Sebastiao, 1987;Barry, 1988) but to a much smaller extent, in low [Ca2"]. (Bennett et al 1990).…”

Section: Discussionmentioning

confidence: 95%

Probabilistic secretion of quanta from nerve terminals in avian ciliary ganglia modulated by adenosine.

Bennett

1991

The Journal of Physiology

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SUMMARY1. The effects of adenosine on the probability of secretion of acetylcholine quanta and on presynaptic and postsynaptic action potentials was examined in the posthatched avian ciliary ganglion.2. Adenosine (20 /tM) reduced the average size of the excitatory postsynaptic potential (EPSP) by 33 %. This was due to a decrease in quantal content of the EPSP (mn). The effect was blocked by theophylline (50 /IM). 4. Plateau-type action potentials with a large calcium component were generated in the ciliary neurones by bathing the ganglion in tetraethylammonium ions (TEA, 10 mM). Adenosine (20 IiM) reduced the duration of these action potentials on short exposures (< 20 min) but increased the duration on longer exposure (> 30 min).Adenosine did not affect the normal action potentiat recorded in the absence of TEA.5. Adenosine (20 ftM) hyperpolarized the nerve terminal and as a consequence increased the size of the presynaptic action potential and reduced its afterhyperpolarization. 6. Plateau-type action potentials with a large calcium component were generated in the nerve terminals using TEA (10 mM). The duration of these action potentials was significantly reduced by adenosine (20 /tM).7. Adenosines action on nerve terminals, to hyperpolarize the membrane and reduce calcium influx, may contribute to its effect in reducing m of the EPSP.

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“…In addition, although it may be true that TMB‐8 was acting as an antagonist to both ryanodine and nicotinic receptors in our studies, there is no evidence suggesting that theophylline is altering transmitter release via the nicotinic receptors or that modest changes in ACh sensitivity will alter the effects of theophylline. The same can be argued for an affect on membrane conductance or protein kinase C activity because these are not relevant to the proposed sites of action of theophylline 20 . Furthermore, an earlier report demonstrated that TMB‐8 alone enhances transmitter release, 15 which is consistent with TMB‐8 antagonizing ryanodine receptors.…”

Section: Discussionmentioning

confidence: 96%

“…Theophylline and its derivative aminophylline have been used extensively to demonstrate the effects of cAMP on neurotransmission owing to their ability to inhibit cyclic nucleotide PDEs 2,5–9 . However, theophylline, in particular, has been shown to both enhance neurotransmitter release from vertebrate motoneurons 2,3 and inhibit transmitter release 15,20,21 . Aminophylline has also been shown to have varying effects on transmitter release 9 .…”

Section: Discussionmentioning

confidence: 99%

EFFECT OF THEOPHYLLINE AND AMINOPHYLLINE ON TRANSMITTER RELEASE AT THE MAMMALIAN NEUROMUSCULAR JUNCTION IS NOT MEDIATED BY cAMP

Nickels

Schwartz

Blevins

et al. 2006

Clin Exp Pharma Physio

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1. Theophylline and aminophylline have been widely used as inhibitors of phosphodiesterase when examining the role of cAMP in regulating cell function. In reality, however, these phosphodiesterase inhibitors may have additional sites of action that could complicate the interpretation of the results. These additional sites of action could include antagonism of inhibitory adenosine autoreceptors and release of intracellular calcium. The purpose of the present study was to determine which of the above three is the primary mechanism by which theophylline and aminophylline affect transmitter release at the mammalian neuromuscular junction. 2. Quantal release measurements were made using intracellular recording techniques. A variety of drugs were used to elucidate this pathway. Isoproterenol, an adenylate cyclase activator, was first used to establish the effect of enhanced levels of cAMP. Theophylline application on its own or in the presence of a drug combination that blocked the adenosine receptor and phosphodiesterase pathways caused significant release depression, opposite to what is expected if it was functioning to enhance cAMP levels. However, when applied in the presence of a drug combination that blocked the adenosine receptor, phosphodiesterase and intracellular ryanodine calcium pathways, theophylline was unable to depress release. Therefore, it was concluded that the major mechanism of action of theophylline is depression of transmitter release by causing the release of intracellular calcium. 3. Aminophylline application alone resulted in a significant enhancement of release. However, when coupled with an adenosine receptor blocker, the ability of aminophylline to enhance transmitter release was blocked, suggesting that its dominant mechanism of action is adenosine receptor inhibition. 4. Taken together, these results indicate that the use of theophylline and aminophylline is inappropriate when examining the role of cAMP at the mammalian neuromuscular junction.

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Dual effects of theophylline on spontaneous transmitter release from frog motor nerve terminals

Cited by 9 publications

References 23 publications

Shaping of monocyte and macrophage function by adenosine receptors

Shaping of monocyte and macrophage function by adenosine receptors

Probabilistic secretion of quanta from nerve terminals in avian ciliary ganglia modulated by adenosine.

EFFECT OF THEOPHYLLINE AND AMINOPHYLLINE ON TRANSMITTER RELEASE AT THE MAMMALIAN NEUROMUSCULAR JUNCTION IS NOT MEDIATED BY cAMP

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