%0 Journal Article %1 Brede2003 %A Brede, M. %A Nagy, G. %A Philipp, M. %A Sorensen, J. B. %A Lohse, M. J. %A Hein, L. %D 2003 %J Mol Endocrinol %K 3-Monooxygenase/metabolism Adrenal Adrenergic Animals Calcium Catecholamines/blood/*metabolism/urine Cells/drug Chromaffin Cultured Epinephrine/blood/metabolism/urine Exocytosis/physiology Feedback, Glands/*metabolism Knockout Mice Nervous Norepinephrine/blood/metabolism/urine Physiological Quinoxalines/pharmacology Signaling/physiology Sympathetic System/*metabolism Tyrosine alpha-2/agonists/genetics/*metabolism alpha-Agonists/pharmacology effects/metabolism Receptor Cell %N 8 %P 1640-6 %T Differential control of adrenal and sympathetic catecholamine release by alpha 2-adrenoceptor subtypes %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12764077 %V 17 %X In the adrenergic system, release of the neurotransmitter norepinephrine from sympathetic nerves is regulated by presynaptic inhibitory alpha2-adrenoceptors, but it is unknown whether release of epinephrine from the adrenal gland is controlled by a similar short feedback loop. Using gene-targeted mice we demonstrate that two distinct subtypes of alpha2-adrenoceptors control release of catecholamines from sympathetic nerves (alpha 2A) and from the adrenal medulla (alpha 2C). In isolated mouse chromaffin cells, alpha2-receptor activation inhibited the electrically stimulated increase in cell capacitance (a correlate of exocytosis), voltage-activated Ca2+ current, as well as secretion of epinephrine and norepinephrine. The inhibitory effects of alpha2-agonists on cell capacitance, voltage-activated Ca2+ currents, and on catecholamine secretion were completely abolished in chromaffin cells isolated from alpha 2C-receptor-deficient mice. In vivo, deletion of sympathetic or adrenal feedback control led to increased plasma and urine norepinephrine (alpha 2A-knockout) and epinephrine levels (alpha 2C-knockout), respectively. Loss of feedback inhibition was compensated by increased tyrosine hydroxylase activity, as detected by elevated tissue dihydroxyphenylalanine levels. Thus, receptor subtype diversity in the adrenergic system has emerged to selectively control sympathetic and adrenal catecholamine secretion via distinct alpha2-adrenoceptor subtypes. Short-loop feedback inhibition of epinephrine release from the adrenal gland may represent a novel therapeutic target for diseases that arise from enhanced adrenergic stimulation.

@article{Brede2003, abstract = {In the adrenergic system, release of the neurotransmitter norepinephrine from sympathetic nerves is regulated by presynaptic inhibitory alpha2-adrenoceptors, but it is unknown whether release of epinephrine from the adrenal gland is controlled by a similar short feedback loop. Using gene-targeted mice we demonstrate that two distinct subtypes of alpha2-adrenoceptors control release of catecholamines from sympathetic nerves (alpha 2A) and from the adrenal medulla (alpha 2C). In isolated mouse chromaffin cells, alpha2-receptor activation inhibited the electrically stimulated increase in cell capacitance (a correlate of exocytosis), voltage-activated Ca2+ current, as well as secretion of epinephrine and norepinephrine. The inhibitory effects of alpha2-agonists on cell capacitance, voltage-activated Ca2+ currents, and on catecholamine secretion were completely abolished in chromaffin cells isolated from alpha 2C-receptor-deficient mice. In vivo, deletion of sympathetic or adrenal feedback control led to increased plasma and urine norepinephrine (alpha 2A-knockout) and epinephrine levels (alpha 2C-knockout), respectively. Loss of feedback inhibition was compensated by increased tyrosine hydroxylase activity, as detected by elevated tissue dihydroxyphenylalanine levels. Thus, receptor subtype diversity in the adrenergic system has emerged to selectively control sympathetic and adrenal catecholamine secretion via distinct alpha2-adrenoceptor subtypes. Short-loop feedback inhibition of epinephrine release from the adrenal gland may represent a novel therapeutic target for diseases that arise from enhanced adrenergic stimulation.}, added-at = {2010-12-14T18:12:02.000+0100}, author = {Brede, M. and Nagy, G. and Philipp, M. and Sorensen, J. B. and Lohse, M. J. and Hein, L.}, biburl = {https://www.bibsonomy.org/bibtex/241a1c48ee8efe5da31aed3dd5b830a36/pharmawuerz}, endnotereftype = {Journal Article}, interhash = {dc5f97fcb562c53e9ae8e878ac65d814}, intrahash = {41a1c48ee8efe5da31aed3dd5b830a36}, issn = {0888-8809 (Print) 0888-8809 (Linking)}, journal = {Mol Endocrinol}, keywords = {3-Monooxygenase/metabolism Adrenal Adrenergic Animals Calcium Catecholamines/blood/*metabolism/urine Cells/drug Chromaffin Cultured Epinephrine/blood/metabolism/urine Exocytosis/physiology Feedback, Glands/*metabolism Knockout Mice Nervous Norepinephrine/blood/metabolism/urine Physiological Quinoxalines/pharmacology Signaling/physiology Sympathetic System/*metabolism Tyrosine alpha-2/agonists/genetics/*metabolism alpha-Agonists/pharmacology effects/metabolism Receptor Cell}, month = Aug, note = {Brede, Marc Nagy, Gabor Philipp, Melanie Sorensen, Jakob B Lohse, Martin J Hein, Lutz Research Support, Non-U.S. Gov't United States Molecular endocrinology (Baltimore, Md.) Mol Endocrinol. 2003 Aug;17(8):1640-6. Epub 2003 May 22.}, number = 8, pages = {1640-6}, shorttitle = {Differential control of adrenal and sympathetic catecholamine release by alpha 2-adrenoceptor subtypes}, timestamp = {2010-12-14T18:22:38.000+0100}, title = {Differential control of adrenal and sympathetic catecholamine release by alpha 2-adrenoceptor subtypes}, url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12764077}, volume = 17, year = 2003 }