Cyclic AMP modulates but does not mediate the inhibition of [3H]norepinephrine release by activation of alpha-2 adrenergic receptors in cultured rat ganglion cells

D. D. Schwartz, Kafait Malik

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Abstract

The purpose of this study was to determine whether a decrease in cyclic AMP accumulation mediates the inhibition of norepinephrine release in response to alpha-2 adrenergic receptor activation in cultured rat superior cervical ganglion cells. Superior cervical ganglia from neonatal rats were dissociated and cultured on collagen-coated plastic strips. Neurotransmitter release was assessed by measuring the fractional overflow of tritium in superfused cells prelabeled with [3H]norepinephrine. Intracellular cyclic AMP accumulation was measured using radioimmunoassay. Electrical field stimulation at 1 Hz, 30 pulses, 1 ms duration at 20 min intervals produced an increase in the fractional overflow of tritium that was composed predominantly of intact [3H]norepinephrine. The alpha-2 adrenergic receptor agonist UK-14,304 dose-dependently attenuated the increase in fractional tritium overflow elicited by electrical field stimulation. The adenylyl cyclase activator, forskolin, increased cyclic AMP accumulation in superior cervical ganglion cells and UK-14,304 dose-dependently inhibited forskolin-stimulated cyclic AMP accumulation. UK-14,304 had no effect on basal cyclic AMP accumulation or cyclic AMP accumulation during electrical field stimulation. Forskolin (1-10 μM) or the non-hydrolysable cAMP analog, 8-(4-chlorophenylthio)adenosine 3′,5′-cyclic monophosphate (1-100 μM), slightly increased basal and dose-dependently potentiated the increase in fractional tritium overflow in response to electrical stimulation. Despite enhancement by forskolin and 8-(4-chlorophenylthio)adenosine 3′,5′-cyclic monophosphate of fractional tritium overflow caused by electrical field stimulation, UK-14304 (1-10 μM) reduced release to a similar degree as that observed in the absence of forskolin or 8-(4-chlorophenylthio)adenosine 3′,5′-cyclic monophosphate. These data suggest that in cultured rat superior cervical ganglion cells, stimulation of alpha-2 adrenergic receptors decreases cyclic AMP accumulation when adenyl cyclase is activated. A decrease in cyclic AMP does not mediate the inhibition of [3H]norepinephrine release in response to alpha-2 adrenergic receptor activation, although elevations in cyclic AMP can enhance electrically-stimulated release of [3H]norepinephrine.

Original languageEnglish (US)
Pages (from-to)107-113
Number of pages7
JournalNeuroscience
Volume52
Issue number1
DOIs
StatePublished - Jan 1 1993

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Adrenergic alpha-2 Receptors
Ganglia
Cyclic AMP
Norepinephrine
Tritium
Colforsin
Superior Cervical Ganglion
Electric Stimulation
Adenosine
Adenylyl Cyclases
Adrenergic alpha-2 Receptor Agonists
Plastics
Radioimmunoassay
Neurotransmitter Agents
Collagen

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

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title = "Cyclic AMP modulates but does not mediate the inhibition of [3H]norepinephrine release by activation of alpha-2 adrenergic receptors in cultured rat ganglion cells",
abstract = "The purpose of this study was to determine whether a decrease in cyclic AMP accumulation mediates the inhibition of norepinephrine release in response to alpha-2 adrenergic receptor activation in cultured rat superior cervical ganglion cells. Superior cervical ganglia from neonatal rats were dissociated and cultured on collagen-coated plastic strips. Neurotransmitter release was assessed by measuring the fractional overflow of tritium in superfused cells prelabeled with [3H]norepinephrine. Intracellular cyclic AMP accumulation was measured using radioimmunoassay. Electrical field stimulation at 1 Hz, 30 pulses, 1 ms duration at 20 min intervals produced an increase in the fractional overflow of tritium that was composed predominantly of intact [3H]norepinephrine. The alpha-2 adrenergic receptor agonist UK-14,304 dose-dependently attenuated the increase in fractional tritium overflow elicited by electrical field stimulation. The adenylyl cyclase activator, forskolin, increased cyclic AMP accumulation in superior cervical ganglion cells and UK-14,304 dose-dependently inhibited forskolin-stimulated cyclic AMP accumulation. UK-14,304 had no effect on basal cyclic AMP accumulation or cyclic AMP accumulation during electrical field stimulation. Forskolin (1-10 μM) or the non-hydrolysable cAMP analog, 8-(4-chlorophenylthio)adenosine 3′,5′-cyclic monophosphate (1-100 μM), slightly increased basal and dose-dependently potentiated the increase in fractional tritium overflow in response to electrical stimulation. Despite enhancement by forskolin and 8-(4-chlorophenylthio)adenosine 3′,5′-cyclic monophosphate of fractional tritium overflow caused by electrical field stimulation, UK-14304 (1-10 μM) reduced release to a similar degree as that observed in the absence of forskolin or 8-(4-chlorophenylthio)adenosine 3′,5′-cyclic monophosphate. These data suggest that in cultured rat superior cervical ganglion cells, stimulation of alpha-2 adrenergic receptors decreases cyclic AMP accumulation when adenyl cyclase is activated. A decrease in cyclic AMP does not mediate the inhibition of [3H]norepinephrine release in response to alpha-2 adrenergic receptor activation, although elevations in cyclic AMP can enhance electrically-stimulated release of [3H]norepinephrine.",
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