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Differential Effects of Epinephrine and Norepinephrine on cAMP Response and Gi3α Protein Expression in Cultured Sympathetic Neurons

Differential Effects of Epinephrine and Norepinephrine on cAMP Response and Gi3α Protein... Abstract The effect of 24-h pretreatment with epinephrine (EPI) or norepinephrine (NE) on α 2 - and β-adrenoceptor agonist-induced, cAMP responses and G i3 α-protein expression was studied in primary cultures of rat superior cervical ganglionic (SCG) neurons. SCG neurons, 10 to 12 days in culture, accumulated cAMP when stimulated with the β-adrenoceptor agonist isoproterenol and the preferential β 2 -adrenoceptor antagonist ICI 118,551 blocked this response. Similarly, the preferential α 2 -adrenoceptor agonist UK14,304 inhibited forskolin-stimulated cAMP accumulation, implying that cultured SCG neurons possess functional α 2 - and β 2 -adrenoceptors. A 24-h treatment of SCG neurons with EPI or NE induced desensitization of the cAMP response to the β-adrenoceptor agonist isoproterenol. Simultaneously, EPI treatment increased the maximal inhibitory cAMP response to the α 2 -adrenoceptor agonist UK14,304 and NE was without effect. Immunoblotting analyses of G i3 α subunits revealed that 24-h EPI but not NE treatment induces a 3- to 4-fold increase in the expression of G i3 α subunits. Furthermore, EPI-induced up-regulation of α-subunit expression can be blocked by the preferential β 2 -adrenoceptor antagonist ICI 118,551 but not by the preferential β 1 -adrenoceptor antagonist CGP 20712A. Our results suggest that changes in α 2 -adrenoceptor responsiveness induced by EPI may involve activation of β 2 -adrenoceptors that influence the expression of inhibitory G proteins. Thus, primary cultures of sympathetic neurons by possessing functional α 2 - and β-adrenoceptors may be a suitable model system to study the signaling mechanisms of “cross talk” between these adrenoceptor subtypes, which are known to play a central role in cardiovascular function. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Pharmacology and Experimental Therapeutics Am. Soc for Pharma & Experimental Therapeutics

Differential Effects of Epinephrine and Norepinephrine on cAMP Response and Gi3α Protein Expression in Cultured Sympathetic Neurons

Differential Effects of Epinephrine and Norepinephrine on cAMP Response and Gi3α Protein Expression in Cultured Sympathetic Neurons

The Journal of Pharmacology and Experimental Therapeutics , Volume 291 (1): 258 – Oct 1, 1999

Abstract

Abstract The effect of 24-h pretreatment with epinephrine (EPI) or norepinephrine (NE) on α 2 - and β-adrenoceptor agonist-induced, cAMP responses and G i3 α-protein expression was studied in primary cultures of rat superior cervical ganglionic (SCG) neurons. SCG neurons, 10 to 12 days in culture, accumulated cAMP when stimulated with the β-adrenoceptor agonist isoproterenol and the preferential β 2 -adrenoceptor antagonist ICI 118,551 blocked this response. Similarly, the preferential α 2 -adrenoceptor agonist UK14,304 inhibited forskolin-stimulated cAMP accumulation, implying that cultured SCG neurons possess functional α 2 - and β 2 -adrenoceptors. A 24-h treatment of SCG neurons with EPI or NE induced desensitization of the cAMP response to the β-adrenoceptor agonist isoproterenol. Simultaneously, EPI treatment increased the maximal inhibitory cAMP response to the α 2 -adrenoceptor agonist UK14,304 and NE was without effect. Immunoblotting analyses of G i3 α subunits revealed that 24-h EPI but not NE treatment induces a 3- to 4-fold increase in the expression of G i3 α subunits. Furthermore, EPI-induced up-regulation of α-subunit expression can be blocked by the preferential β 2 -adrenoceptor antagonist ICI 118,551 but not by the preferential β 1 -adrenoceptor antagonist CGP 20712A. Our results suggest that changes in α 2 -adrenoceptor responsiveness induced by EPI may involve activation of β 2 -adrenoceptors that influence the expression of inhibitory G proteins. Thus, primary cultures of sympathetic neurons by possessing functional α 2 - and β-adrenoceptors may be a suitable model system to study the signaling mechanisms of “cross talk” between these adrenoceptor subtypes, which are known to play a central role in cardiovascular function.

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Publisher
Am. Soc for Pharma & Experimental Therapeutics
Copyright
Copyright © Journal of Pharmacology and Experimental Therapeutics
ISSN
0022-3565
eISSN
1521-0103
Publisher site

Abstract

Abstract The effect of 24-h pretreatment with epinephrine (EPI) or norepinephrine (NE) on α 2 - and β-adrenoceptor agonist-induced, cAMP responses and G i3 α-protein expression was studied in primary cultures of rat superior cervical ganglionic (SCG) neurons. SCG neurons, 10 to 12 days in culture, accumulated cAMP when stimulated with the β-adrenoceptor agonist isoproterenol and the preferential β 2 -adrenoceptor antagonist ICI 118,551 blocked this response. Similarly, the preferential α 2 -adrenoceptor agonist UK14,304 inhibited forskolin-stimulated cAMP accumulation, implying that cultured SCG neurons possess functional α 2 - and β 2 -adrenoceptors. A 24-h treatment of SCG neurons with EPI or NE induced desensitization of the cAMP response to the β-adrenoceptor agonist isoproterenol. Simultaneously, EPI treatment increased the maximal inhibitory cAMP response to the α 2 -adrenoceptor agonist UK14,304 and NE was without effect. Immunoblotting analyses of G i3 α subunits revealed that 24-h EPI but not NE treatment induces a 3- to 4-fold increase in the expression of G i3 α subunits. Furthermore, EPI-induced up-regulation of α-subunit expression can be blocked by the preferential β 2 -adrenoceptor antagonist ICI 118,551 but not by the preferential β 1 -adrenoceptor antagonist CGP 20712A. Our results suggest that changes in α 2 -adrenoceptor responsiveness induced by EPI may involve activation of β 2 -adrenoceptors that influence the expression of inhibitory G proteins. Thus, primary cultures of sympathetic neurons by possessing functional α 2 - and β-adrenoceptors may be a suitable model system to study the signaling mechanisms of “cross talk” between these adrenoceptor subtypes, which are known to play a central role in cardiovascular function.

Journal

The Journal of Pharmacology and Experimental TherapeuticsAm. Soc for Pharma & Experimental Therapeutics

Published: Oct 1, 1999

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