Chronic exposure to adenosine receptor agonists and antagonists reciprocally regulates the A1 adenosine receptor-adenylyl cyclase system in cerebellar granule cells

Barbara D. Hettinger-Smith, Mark Leid, Thomas F. Murray

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44 Citations (Scopus)

Abstract

Chronic treatment with the adenosine receptor antagonist caffeine evokes an up-regulation of A1 adenosine receptors and increased coupling of the receptor to G proteins in rat brain membranes. However, chronic agonist exposure has not been explored. Primary cultures of cerebellar granule cells were exposed chronically to A1 adenosine receptor agonists and antagonists. Exposure to the A1 adenosine receptor agonist N6-cyclopentyladenosine resulted in (1) a time- and concentration-dependent reduction in the density of receptors labeled by 1,3[3H]dipropyl-8-cyclopentylxanthine, (2) an enhanced ability of guanyl nucleotides to decrease the fraction of A1 adenosine receptor sites displaying high affinity for 2-chloroadenosine, and (3) a functional uncoupling of receptors from adenylyl cyclase (EC 4.6.1.1). The adenosine antagonists caffeine and 8-p-sulfophenyltheophylline produced alterations in A1 adenosine receptor homeostasis that were antipodal to those associated with agonist treatment. Antagonist exposure (1) increased the density of A1 adenosine receptors in cerebellar granule cell membranes, (2) blunted the effect of guanyl nucleotides on receptor coupling to G proteins, and (3) increased the functional coupling of receptors to adenylyl cyclase inhibition. Forskolin treatment of cerebellar granule cells did not affect receptor density, suggesting that cyclic AMP is not involved in the regulation of A1 adenosine receptor expression.

Original languageEnglish
Pages (from-to)1921-1930
Number of pages10
JournalJournal of Neurochemistry
Volume67
Issue number5
StatePublished - Nov 1996
Externally publishedYes

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Purinergic P1 Receptor Agonists
Purinergic P1 Receptor Antagonists
Adenosine A1 Receptors
Adenylyl Cyclases
Adenosine A1 Receptor Agonists
Caffeine
GTP-Binding Proteins
Nucleotides
Adenosine A1 Receptor Antagonists
2-Chloroadenosine
Colforsin
Cell membranes
Cyclic AMP
Adenosine
Rats
Brain
Homeostasis
Up-Regulation
Cell Membrane
Membranes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

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abstract = "Chronic treatment with the adenosine receptor antagonist caffeine evokes an up-regulation of A1 adenosine receptors and increased coupling of the receptor to G proteins in rat brain membranes. However, chronic agonist exposure has not been explored. Primary cultures of cerebellar granule cells were exposed chronically to A1 adenosine receptor agonists and antagonists. Exposure to the A1 adenosine receptor agonist N6-cyclopentyladenosine resulted in (1) a time- and concentration-dependent reduction in the density of receptors labeled by 1,3[3H]dipropyl-8-cyclopentylxanthine, (2) an enhanced ability of guanyl nucleotides to decrease the fraction of A1 adenosine receptor sites displaying high affinity for 2-chloroadenosine, and (3) a functional uncoupling of receptors from adenylyl cyclase (EC 4.6.1.1). The adenosine antagonists caffeine and 8-p-sulfophenyltheophylline produced alterations in A1 adenosine receptor homeostasis that were antipodal to those associated with agonist treatment. Antagonist exposure (1) increased the density of A1 adenosine receptors in cerebellar granule cell membranes, (2) blunted the effect of guanyl nucleotides on receptor coupling to G proteins, and (3) increased the functional coupling of receptors to adenylyl cyclase inhibition. Forskolin treatment of cerebellar granule cells did not affect receptor density, suggesting that cyclic AMP is not involved in the regulation of A1 adenosine receptor expression.",
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T1 - Chronic exposure to adenosine receptor agonists and antagonists reciprocally regulates the A1 adenosine receptor-adenylyl cyclase system in cerebellar granule cells

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AU - Leid, Mark

AU - Murray, Thomas F.

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N2 - Chronic treatment with the adenosine receptor antagonist caffeine evokes an up-regulation of A1 adenosine receptors and increased coupling of the receptor to G proteins in rat brain membranes. However, chronic agonist exposure has not been explored. Primary cultures of cerebellar granule cells were exposed chronically to A1 adenosine receptor agonists and antagonists. Exposure to the A1 adenosine receptor agonist N6-cyclopentyladenosine resulted in (1) a time- and concentration-dependent reduction in the density of receptors labeled by 1,3[3H]dipropyl-8-cyclopentylxanthine, (2) an enhanced ability of guanyl nucleotides to decrease the fraction of A1 adenosine receptor sites displaying high affinity for 2-chloroadenosine, and (3) a functional uncoupling of receptors from adenylyl cyclase (EC 4.6.1.1). The adenosine antagonists caffeine and 8-p-sulfophenyltheophylline produced alterations in A1 adenosine receptor homeostasis that were antipodal to those associated with agonist treatment. Antagonist exposure (1) increased the density of A1 adenosine receptors in cerebellar granule cell membranes, (2) blunted the effect of guanyl nucleotides on receptor coupling to G proteins, and (3) increased the functional coupling of receptors to adenylyl cyclase inhibition. Forskolin treatment of cerebellar granule cells did not affect receptor density, suggesting that cyclic AMP is not involved in the regulation of A1 adenosine receptor expression.

AB - Chronic treatment with the adenosine receptor antagonist caffeine evokes an up-regulation of A1 adenosine receptors and increased coupling of the receptor to G proteins in rat brain membranes. However, chronic agonist exposure has not been explored. Primary cultures of cerebellar granule cells were exposed chronically to A1 adenosine receptor agonists and antagonists. Exposure to the A1 adenosine receptor agonist N6-cyclopentyladenosine resulted in (1) a time- and concentration-dependent reduction in the density of receptors labeled by 1,3[3H]dipropyl-8-cyclopentylxanthine, (2) an enhanced ability of guanyl nucleotides to decrease the fraction of A1 adenosine receptor sites displaying high affinity for 2-chloroadenosine, and (3) a functional uncoupling of receptors from adenylyl cyclase (EC 4.6.1.1). The adenosine antagonists caffeine and 8-p-sulfophenyltheophylline produced alterations in A1 adenosine receptor homeostasis that were antipodal to those associated with agonist treatment. Antagonist exposure (1) increased the density of A1 adenosine receptors in cerebellar granule cell membranes, (2) blunted the effect of guanyl nucleotides on receptor coupling to G proteins, and (3) increased the functional coupling of receptors to adenylyl cyclase inhibition. Forskolin treatment of cerebellar granule cells did not affect receptor density, suggesting that cyclic AMP is not involved in the regulation of A1 adenosine receptor expression.

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