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

doi:10.1016/0306-4522(93)90186-J

Neuroscience

Volume 52, Issue 1, January 1993, Pages 107-113

https://doi.org/10.1016/0306-4522(93)90186-J Get rights and content

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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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

Eur. J. Pharmac.

Trends pharmac. Sci.

Biochem. Pharmac.

Meth. Enzym.

J. biol. Chem.

Prog. Biophys. molec. Biol.

Metabolism of norepinephrine release by phenoxybenzamine in isolated guinea pig atria

J. Pharmac. exp. Ther.

Role of adenosine 3′,5′-cyclic monophosphate in adrenoceptor-mediated control of3H-noradrenaline secretion in guinea-pig ileum myenteric nerve terminals

Naunyn-Schmiedeberg's Arch. Pharmac.

A study of the factors affecting the aluminum oxide trihydroxyindole procedure for analysis of catecholamines

J. Pharmac. exp. Ther.

Radioimmunoassay of cyclic AMP and cyclic GMP

Role of cyclic AMP in the prejunctional alpha-2 adrenoceptor modulation of noradrenaline release from rat tail artery

Naunyn-Schmiedeberg's Arch. Pharmac.

Alpha-2A and alpha-2B adrenergic receptor subtypes: attenuation of cyclic AMP production in cell lines containing only one receptor subtype

J. Pharmac. exp. Ther.

Release of norepinephrine and dopamine-beta-hydroxylase by nerve stimulation. IV. An evaluation of a role for cyclic adenosine monophosphate

J. Pharmac. exp. Ther.

Depolarization-dependent protein phosphorylation in rat cortical synaptosomes; characterization of active protein kinases by phosphopeptide analysis of substrates

J. Neurochem.

Involvement of cAMP in modulation of noradrenaline release in human pulmonary artery

Naunyn-Schmiedeberg's Arch. Pharmac.

Inhibition of adenylate cyclase by hormones and neurotransmitters

Adv. Cyclic Nucleotide Res.

Involvement of cyclic nucleotides in prejunctional modulation of noradrenaline release in mouse atria

Br. J. Pharmac.

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

Role of adenosine 3′,5′-cyclic monophosphate in adrenoceptor-mediated control of³H-noradrenaline secretion in guinea-pig ileum myenteric nerve terminals