Cyclic AMP accumulation in rat soleus muscle: Stimulation by β2- but not β3-adrenoceptors

Susan J. Roberts, Roger J. Summers

Research output: Contribution to journalArticleResearchpeer-review

Abstract

The β-adrenoceptor subtypes involved in cyclic AMP accumulation in rat soleus muscle were studied using β1- β2- and β3-adrenoceptor agonists and antagonists. Responses to (-)-isoprenaline were antagonised by (-)- propranolol (pK(B) = 8.32 at 0.1 μM) and by erythro-DL-1(7-methylindian-4- yloxy)-3-isopropylaminobutan-2-ol ((±)-ICI 118551) (pK(B) = 9.38 at 10 nM and 9.65 at 100 nM) but not by 2-hydroxy-5(2-((2-hydroxy-3-(4-((1-methyl-4- trifluoromethyl)1H-imidazole-2-yl)-phenoxy)propyl)amino)ethoxy)-benzamide monomethane sulfonate ((±)-CGP 20712A at 10 nM or 100 nM). The β3- adrenoceptor agonist sodium-4-[-2[-2-hydroxy-2-(-3- chlorophenyl)ethylamino]propyl]phenoxyacetate (BRL 37344 at 10 pM or 10 μM) caused no significant change in basal cyclic AMP levels and had no effect on the level of cyclic AMP accumulation stimulated by (-)-isoprenaline, zinterol or forskolin. (-)-Isoprenaline pretreatment (400 μg kg-1 h-1, 14 days) abolished responses to (-)-isoprenaline (10 μM) and zinterol (1 μM) while BRL 37344 had no effect in either isoprenaline or vehicle-treated groups. These results show that β3-adrenoceptor agonists do not stimulate cyclic AMP accumulation in rat soleus muscle and that (-)-isoprenaline induced increases in cyclic AMP levels are mediated predominantly by β2- adrenoceptors. This suggests that the previously reported increase in glucose uptake by β3-adrenoceptor agonists in skeletal muscle does not involve direct stimulation of adenylate cyclase.

Original languageEnglish
Pages (from-to)53-60
Number of pages8
JournalEuropean Journal of Pharmacology
Volume348
Issue number1
DOIs
Publication statusPublished - 1 May 1998
Externally publishedYes

Keywords

  • β-adrenoceptor
  • (Regulation)
  • BRL 37344
  • CAMP
  • Soleus muscle

Cite this

@article{4aad630dc63b4b2295914527ef7f5581,
title = "Cyclic AMP accumulation in rat soleus muscle: Stimulation by β2- but not β3-adrenoceptors",
abstract = "The β-adrenoceptor subtypes involved in cyclic AMP accumulation in rat soleus muscle were studied using β1- β2- and β3-adrenoceptor agonists and antagonists. Responses to (-)-isoprenaline were antagonised by (-)- propranolol (pK(B) = 8.32 at 0.1 μM) and by erythro-DL-1(7-methylindian-4- yloxy)-3-isopropylaminobutan-2-ol ((±)-ICI 118551) (pK(B) = 9.38 at 10 nM and 9.65 at 100 nM) but not by 2-hydroxy-5(2-((2-hydroxy-3-(4-((1-methyl-4- trifluoromethyl)1H-imidazole-2-yl)-phenoxy)propyl)amino)ethoxy)-benzamide monomethane sulfonate ((±)-CGP 20712A at 10 nM or 100 nM). The β3- adrenoceptor agonist sodium-4-[-2[-2-hydroxy-2-(-3- chlorophenyl)ethylamino]propyl]phenoxyacetate (BRL 37344 at 10 pM or 10 μM) caused no significant change in basal cyclic AMP levels and had no effect on the level of cyclic AMP accumulation stimulated by (-)-isoprenaline, zinterol or forskolin. (-)-Isoprenaline pretreatment (400 μg kg-1 h-1, 14 days) abolished responses to (-)-isoprenaline (10 μM) and zinterol (1 μM) while BRL 37344 had no effect in either isoprenaline or vehicle-treated groups. These results show that β3-adrenoceptor agonists do not stimulate cyclic AMP accumulation in rat soleus muscle and that (-)-isoprenaline induced increases in cyclic AMP levels are mediated predominantly by β2- adrenoceptors. This suggests that the previously reported increase in glucose uptake by β3-adrenoceptor agonists in skeletal muscle does not involve direct stimulation of adenylate cyclase.",
keywords = "β-adrenoceptor, (Regulation), BRL 37344, CAMP, Soleus muscle",
author = "Roberts, {Susan J.} and Summers, {Roger J.}",
year = "1998",
month = "5",
day = "1",
doi = "10.1016/S0014-2999(98)00021-1",
language = "English",
volume = "348",
pages = "53--60",
journal = "European Journal of Pharmacology",
issn = "0014-2999",
publisher = "Elsevier",
number = "1",

}

Cyclic AMP accumulation in rat soleus muscle : Stimulation by β2- but not β3-adrenoceptors. / Roberts, Susan J.; Summers, Roger J.

In: European Journal of Pharmacology, Vol. 348, No. 1, 01.05.1998, p. 53-60.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Cyclic AMP accumulation in rat soleus muscle

T2 - Stimulation by β2- but not β3-adrenoceptors

AU - Roberts, Susan J.

AU - Summers, Roger J.

PY - 1998/5/1

Y1 - 1998/5/1

N2 - The β-adrenoceptor subtypes involved in cyclic AMP accumulation in rat soleus muscle were studied using β1- β2- and β3-adrenoceptor agonists and antagonists. Responses to (-)-isoprenaline were antagonised by (-)- propranolol (pK(B) = 8.32 at 0.1 μM) and by erythro-DL-1(7-methylindian-4- yloxy)-3-isopropylaminobutan-2-ol ((±)-ICI 118551) (pK(B) = 9.38 at 10 nM and 9.65 at 100 nM) but not by 2-hydroxy-5(2-((2-hydroxy-3-(4-((1-methyl-4- trifluoromethyl)1H-imidazole-2-yl)-phenoxy)propyl)amino)ethoxy)-benzamide monomethane sulfonate ((±)-CGP 20712A at 10 nM or 100 nM). The β3- adrenoceptor agonist sodium-4-[-2[-2-hydroxy-2-(-3- chlorophenyl)ethylamino]propyl]phenoxyacetate (BRL 37344 at 10 pM or 10 μM) caused no significant change in basal cyclic AMP levels and had no effect on the level of cyclic AMP accumulation stimulated by (-)-isoprenaline, zinterol or forskolin. (-)-Isoprenaline pretreatment (400 μg kg-1 h-1, 14 days) abolished responses to (-)-isoprenaline (10 μM) and zinterol (1 μM) while BRL 37344 had no effect in either isoprenaline or vehicle-treated groups. These results show that β3-adrenoceptor agonists do not stimulate cyclic AMP accumulation in rat soleus muscle and that (-)-isoprenaline induced increases in cyclic AMP levels are mediated predominantly by β2- adrenoceptors. This suggests that the previously reported increase in glucose uptake by β3-adrenoceptor agonists in skeletal muscle does not involve direct stimulation of adenylate cyclase.

AB - The β-adrenoceptor subtypes involved in cyclic AMP accumulation in rat soleus muscle were studied using β1- β2- and β3-adrenoceptor agonists and antagonists. Responses to (-)-isoprenaline were antagonised by (-)- propranolol (pK(B) = 8.32 at 0.1 μM) and by erythro-DL-1(7-methylindian-4- yloxy)-3-isopropylaminobutan-2-ol ((±)-ICI 118551) (pK(B) = 9.38 at 10 nM and 9.65 at 100 nM) but not by 2-hydroxy-5(2-((2-hydroxy-3-(4-((1-methyl-4- trifluoromethyl)1H-imidazole-2-yl)-phenoxy)propyl)amino)ethoxy)-benzamide monomethane sulfonate ((±)-CGP 20712A at 10 nM or 100 nM). The β3- adrenoceptor agonist sodium-4-[-2[-2-hydroxy-2-(-3- chlorophenyl)ethylamino]propyl]phenoxyacetate (BRL 37344 at 10 pM or 10 μM) caused no significant change in basal cyclic AMP levels and had no effect on the level of cyclic AMP accumulation stimulated by (-)-isoprenaline, zinterol or forskolin. (-)-Isoprenaline pretreatment (400 μg kg-1 h-1, 14 days) abolished responses to (-)-isoprenaline (10 μM) and zinterol (1 μM) while BRL 37344 had no effect in either isoprenaline or vehicle-treated groups. These results show that β3-adrenoceptor agonists do not stimulate cyclic AMP accumulation in rat soleus muscle and that (-)-isoprenaline induced increases in cyclic AMP levels are mediated predominantly by β2- adrenoceptors. This suggests that the previously reported increase in glucose uptake by β3-adrenoceptor agonists in skeletal muscle does not involve direct stimulation of adenylate cyclase.

KW - β-adrenoceptor

KW - (Regulation)

KW - BRL 37344

KW - CAMP

KW - Soleus muscle

UR - http://www.scopus.com/inward/record.url?scp=0032077046&partnerID=8YFLogxK

U2 - 10.1016/S0014-2999(98)00021-1

DO - 10.1016/S0014-2999(98)00021-1

M3 - Article

VL - 348

SP - 53

EP - 60

JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

SN - 0014-2999

IS - 1

ER -