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Article: Desensitization of the histamine H1-receptor and transcriptional down-regulation of histamine H1-receptor gene expression in bovine tracheal smooth muscle

TitleDesensitization of the histamine H1-receptor and transcriptional down-regulation of histamine H1-receptor gene expression in bovine tracheal smooth muscle
Authors
Issue Date1998
PublisherJohn Wiley & Sons Ltd. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=0007-1188&site=1
Citation
British Journal Of Pharmacology, 1998, v. 125 n. 7, p. 1477-1484 How to Cite?
Abstract1. We have investigated the role of protein kinase C (PKC) in the desensitization of histamine H1-receptors and in the expression of the histamine H1-receptor gene in airway smooth muscle. 2. Prolonged 4β-phorbol 12,13 dibutyrate (PDBu) pretreatment (4 h, 100 nM-1 μM) of bovine trachealis caused a concentration-dependent loss of contraction in response to histamine H1-receptor stimulation, which was associated with a concentration-dependent decrease in histamine-induced total [3H]-inositol phosphates accumulation. In contrast, the responses to sodium fluoride, a direct G-protein activator, were unalterd by PDBu (100-300 nM) pre-incubation and only slightly reduced following incubation with 1 μM PDBu. 3. A selective PKC inhibitor, GF 109203X, partially blocked the PDBu (1 μM)-induced desensitization and completely blocked the effect of 100 nM PDBu, confirming the involvement of PKC. 4. Binding experiments using [3H]-pyrilamine revealed a class of high-affinity binding sites within the range for the histamine H1 receptor in airway smooth muscle. PDBu (1 μM) pretreatment for 4 h did not change the number of histamine H1 receptors. 5. PDBu (1 μM) exposure caused a time-dependent reduction in the steady-state levels of histamine H1-receptor mRNA, which was inhibited by pre-incubation with GF 109203X and by cycloheximide, a protein synthesis inhibitor. 6. Nuclear run-on assays revealed a 50% reduction in the rate of histamine H1-receptor gene transcription after 17 h PDBu pretreatment, whereas mRNA stability was not affected by PDBu pretreatment (17 h). 7. In conclusion, we have shown a PKC-mediated desensitization of the histamine H1-receptor in BTSM and a transcriptional down-regulation of the histamine H1-receptor gene expression, which requires new protein synthesis.
Persistent Identifierhttp://hdl.handle.net/10722/162216
ISSN
2015 Impact Factor: 5.259
2015 SCImago Journal Rankings: 2.368
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorPype, JLen_US
dc.contributor.authorMak, JCWen_US
dc.contributor.authorDupont, LJen_US
dc.contributor.authorVerleden, GMen_US
dc.contributor.authorBarnes, PJen_US
dc.date.accessioned2012-09-05T05:18:10Z-
dc.date.available2012-09-05T05:18:10Z-
dc.date.issued1998en_US
dc.identifier.citationBritish Journal Of Pharmacology, 1998, v. 125 n. 7, p. 1477-1484en_US
dc.identifier.issn0007-1188en_US
dc.identifier.urihttp://hdl.handle.net/10722/162216-
dc.description.abstract1. We have investigated the role of protein kinase C (PKC) in the desensitization of histamine H1-receptors and in the expression of the histamine H1-receptor gene in airway smooth muscle. 2. Prolonged 4β-phorbol 12,13 dibutyrate (PDBu) pretreatment (4 h, 100 nM-1 μM) of bovine trachealis caused a concentration-dependent loss of contraction in response to histamine H1-receptor stimulation, which was associated with a concentration-dependent decrease in histamine-induced total [3H]-inositol phosphates accumulation. In contrast, the responses to sodium fluoride, a direct G-protein activator, were unalterd by PDBu (100-300 nM) pre-incubation and only slightly reduced following incubation with 1 μM PDBu. 3. A selective PKC inhibitor, GF 109203X, partially blocked the PDBu (1 μM)-induced desensitization and completely blocked the effect of 100 nM PDBu, confirming the involvement of PKC. 4. Binding experiments using [3H]-pyrilamine revealed a class of high-affinity binding sites within the range for the histamine H1 receptor in airway smooth muscle. PDBu (1 μM) pretreatment for 4 h did not change the number of histamine H1 receptors. 5. PDBu (1 μM) exposure caused a time-dependent reduction in the steady-state levels of histamine H1-receptor mRNA, which was inhibited by pre-incubation with GF 109203X and by cycloheximide, a protein synthesis inhibitor. 6. Nuclear run-on assays revealed a 50% reduction in the rate of histamine H1-receptor gene transcription after 17 h PDBu pretreatment, whereas mRNA stability was not affected by PDBu pretreatment (17 h). 7. In conclusion, we have shown a PKC-mediated desensitization of the histamine H1-receptor in BTSM and a transcriptional down-regulation of the histamine H1-receptor gene expression, which requires new protein synthesis.en_US
dc.languageengen_US
dc.publisherJohn Wiley & Sons Ltd. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=0007-1188&site=1en_US
dc.relation.ispartofBritish Journal of Pharmacologyen_US
dc.subject.meshAnimalsen_US
dc.subject.meshBlotting, Northernen_US
dc.subject.meshCattleen_US
dc.subject.meshDose-Response Relationship, Drugen_US
dc.subject.meshDown-Regulationen_US
dc.subject.meshEnzyme Activationen_US
dc.subject.meshEnzyme Inhibitors - Pharmacologyen_US
dc.subject.meshGene Expression Regulation - Drug Effectsen_US
dc.subject.meshHistamineen_US
dc.subject.meshIndoles - Pharmacologyen_US
dc.subject.meshInositol Phosphates - Metabolismen_US
dc.subject.meshMaleimides - Pharmacologyen_US
dc.subject.meshMuscle Contraction - Drug Effectsen_US
dc.subject.meshMuscle, Smooth - Drug Effects - Metabolismen_US
dc.subject.meshPhorbol 12,13-Dibutyrate - Pharmacologyen_US
dc.subject.meshProtein Kinase C - Antagonists & Inhibitors - Metabolismen_US
dc.subject.meshReceptors, Histamine H1 - Genetics - Metabolismen_US
dc.subject.meshSodium Fluoride - Pharmacologyen_US
dc.subject.meshTrachea - Metabolismen_US
dc.subject.meshTranscription, Genetic - Drug Effectsen_US
dc.subject.meshTritiumen_US
dc.titleDesensitization of the histamine H1-receptor and transcriptional down-regulation of histamine H1-receptor gene expression in bovine tracheal smooth muscleen_US
dc.typeArticleen_US
dc.identifier.emailMak, JCW:judymak@hku.hken_US
dc.identifier.authorityMak, JCW=rp00352en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1038/sj.bjp.0702222-
dc.identifier.pmid9884076-
dc.identifier.scopuseid_2-s2.0-0031593619en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0031593619&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume125en_US
dc.identifier.issue7en_US
dc.identifier.spage1477en_US
dc.identifier.epage1484en_US
dc.identifier.isiWOS:000077417600013-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridPype, JL=6602509935en_US
dc.identifier.scopusauthoridMak, JCW=7103323094en_US
dc.identifier.scopusauthoridDupont, LJ=7102011073en_US
dc.identifier.scopusauthoridVerleden, GM=7006513432en_US
dc.identifier.scopusauthoridBarnes, PJ=36064679400en_US

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