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dc.contributor.advisorAbel, Peter W.en_US
dc.contributor.authorBruchas, Michael Raymonden_US
dc.date.accessioned2014-11-17T15:36:12Z
dc.date.available2014-11-17T15:36:12Z
dc.date.issued2004-06en_US
dc.identifier.urihttp://hdl.handle.net/10504/63698
dc.description.abstractRecently an immortalized epithelial ceil line, SMG-C10, was isolated from rat submandibular gland cells. We compared the pharmacological characteristics of ar AR in SMG-C10 cells using [125I]BE 2254. The subtype-selective antagonists 5- methyurapidil (a-1A selective), BMY 7378 (a-1D selective), and chloroethylclonidine (CEC) (a-1e selective) were used to determine a1-AR subtype expression in the rat submandibular gland and SMG-C10 cells. Affinities (Ki’s) in SMG-C10 and for 5- methylurapidil (KiH = 0.64 nM and KiL = 91 nM ) were consistent with binding sites for the aiA-AR and the a1B-AR. CEC treatment followed by saturation binding revealed a population of a1-ARs sensitive to CEC at conditions selective for the otiB- AR Western blotting for phosphorylation of ERK 1/2 was used to determine whether the aiB-ARs in SMG-C10 couple to mitogen-activated protein kinase pathways. Using arAR subtype-selective antagonists it was determined that phenylephrine (10-100pM) stimulated ERK 1/2 phosphorylation (4-5 fold over basal) was mediated by the aiB-AR subtype. We also used the aiA-AR subtype selective antagonist A 61603 and confirmed that the a1a-AR does not activate ERK 1/2 in SMG-C10 cells. Furthermore, the aiB-AR stimulated ERK 1/2 phosphorylation was attenuated by the cholesterol inhibitors filipin and methyl-p-cyclodextrin. Prelimary experiments also demonstrated the a1-ARs in SMG-C10 cells can activate p38 but do not activate JNK. These data suggest that ai-ARs may couple to distinct signaling pathways in SMG-C10 cells and furthermore that the SMG-C10 cells may provide a useful model to study a1B-AR signaling in submandibular glands.en_US
dc.language.isoen_USen_US
dc.publisherCreighton Universityen_US
dc.rightsCopyright is retained by the Author. A non-exclusive distribution right is granted to Creighton University and to ProQuest following the publishing model selected above.en_US
dc.subject.meshReceptors, Adrenergic, alpha-1en_US
dc.titlePharmacological Studies Of Alpha-1 Adrenergic Receptorsen_US
dc.typeDissertation
dc.rights.holderMichael Raymond Bruchasen_US
dc.publisher.locationOmaha, Nebraskaen_US
dc.description.noteProQuest Traditional Publishing Optionen_US
dc.description.pagesxvii, 122 pagesen_US
dc.contributor.cuauthorBruchas, Michael Raymonden_US
dc.degree.levelPhD (Doctor of Philosophy)en_US
dc.degree.disciplinePharmacology (graduate program)en_US
dc.degree.namePh.D. in Pharmacologyen_US
dc.degree.grantorGraduate Schoolen_US
dc.degree.committeeBockman, Charles S.en_US
dc.degree.committeeToews, Myronen_US
dc.degree.committeeScofield, Margaret A.en_US
dc.degree.committeeJeffries, Williamen_US


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