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Modulation of voltage-dependant Ba2+ currents in the guinea-pig gastric antrum by cyclic nucleotide-dependent pathways

Zhu, Hai-Lei; Hirst, George; Ito, Yushi; Teramoto, Noriyoshi

Description

We have investigated whether the activation of cAMP- and cGMP-dependent pathways modifies the properties of voltage-dependent Ba 2+ currents (I Ba) recorded from guinea-pig gastric myocytes using patch-clamp techniques. All experiments were carried on single smooth muscle cells, dispersed from the circular layer of the guinea-pig gastric antrum. Both dibutyryl cAMP (db-cAMP, 0.1-1 mM), a membrane-permeable ester of cAMP, and isoproterenol, a selective β-stimulant, inhibited I Ba in a...[Show more]

dc.contributor.authorZhu, Hai-Lei
dc.contributor.authorHirst, George
dc.contributor.authorIto, Yushi
dc.contributor.authorTeramoto, Noriyoshi
dc.date.accessioned2015-12-13T23:00:06Z
dc.identifier.issn0007-1188
dc.identifier.urihttp://hdl.handle.net/1885/83985
dc.description.abstractWe have investigated whether the activation of cAMP- and cGMP-dependent pathways modifies the properties of voltage-dependent Ba 2+ currents (I Ba) recorded from guinea-pig gastric myocytes using patch-clamp techniques. All experiments were carried on single smooth muscle cells, dispersed from the circular layer of the guinea-pig gastric antrum. Both dibutyryl cAMP (db-cAMP, 0.1-1 mM), a membrane-permeable ester of cAMP, and isoproterenol, a selective β-stimulant, inhibited I Ba in a concentration-dependent manner. Forskolin, but not dideoxy-forskolin, an inactive isomer of forskolin, inhibited the peak amplitude of I Ba. In the presence of either Rp-cAMP or the PKA (cAMP-dependent protein kinase) inhibitor peptide 5-24 (PKA-IP), neither forskolin nor db-cAMP inhibited I Ba. After establishing a conventional whole-cell recording, the peak amplitude of I Ba gradually decreased when the catalytic subunit of PKA was included in the pipette. The further application of Rp-cAMP reversibly enhanced I Ba. Sodium nitroprusside (0.1-1 mM) and 8-Br-cGMP (0.1-1 mM) also inhibited I Ba in a concentration-dependent manner. The inhibitory effects of forskolin or db-cAMP on I Ba were not significantly changed by pretreatment with a cGMP-dependent protein kinase (PKG) inhibitor. Similarly, the inhibitory actions of 8-Br-cGMP on I Ba were not modified by PKA-IP. The membrane-permeable cyclic nucleotides db-cAMP and 8-Br-cGMP caused little shift of the voltage dependence of the steady-state inactivation and reactivation curves. Neither of the membrane-permeable cyclic nucleotides db-cAMP or 8-Br-cGMP had additive inhibitory effects on I Ba. These results indicate that two distinct cyclic nucleotide-dependent pathways are present in the guinea-pig gastric antrum, and that both inhibited I Ba in an independent manner.
dc.publisherNature Publishing Group
dc.sourceBritish Journal of Pharmacology
dc.subjectKeywords: 8 bromo cyclic AMP; beta adrenergic receptor stimulating agent; bucladesine; cyclic AMP; cyclic AMP dependent protein kinase inhibitor; cyclic GMP; cyclic nucleotide dependent protein kinase; forskolin; isoprenaline; nitroprusside sodium; voltage gated ca Cyclic nucleotide; Gastrointestinal smooth muscle; Voltage-dependent calcium channels
dc.titleModulation of voltage-dependant Ba2+ currents in the guinea-pig gastric antrum by cyclic nucleotide-dependent pathways
dc.typeJournal article
local.description.notesImported from ARIES
local.description.refereedYes
local.identifier.citationvolume146
dc.date.issued2005
local.identifier.absfor110901 - Autonomic Nervous System
local.identifier.ariespublicationMigratedxPub12254
local.type.statusPublished Version
local.contributor.affiliationZhu, Hai-Lei, Kyusha University
local.contributor.affiliationHirst, George, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationIto, Yushi, Kyusha University
local.contributor.affiliationTeramoto, Noriyoshi, Kyusha University
local.description.embargo2037-12-31
local.bibliographicCitation.startpage129
local.bibliographicCitation.lastpage138
local.identifier.doi10.1038/sj.bjp.0706295
dc.date.updated2015-12-12T07:32:16Z
local.identifier.scopusID2-s2.0-30644462833
CollectionsANU Research Publications

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