Modulation of voltage-dependant Ba2+ currents in the guinea-pig gastric antrum by cyclic nucleotide-dependent pathways
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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.author | Zhu, Hai-Lei | |
---|---|---|
dc.contributor.author | Hirst, George | |
dc.contributor.author | Ito, Yushi | |
dc.contributor.author | Teramoto, Noriyoshi | |
dc.date.accessioned | 2015-12-13T23:00:06Z | |
dc.identifier.issn | 0007-1188 | |
dc.identifier.uri | http://hdl.handle.net/1885/83985 | |
dc.description.abstract | 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 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.publisher | Nature Publishing Group | |
dc.source | British Journal of Pharmacology | |
dc.subject | Keywords: 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.title | Modulation of voltage-dependant Ba2+ currents in the guinea-pig gastric antrum by cyclic nucleotide-dependent pathways | |
dc.type | Journal article | |
local.description.notes | Imported from ARIES | |
local.description.refereed | Yes | |
local.identifier.citationvolume | 146 | |
dc.date.issued | 2005 | |
local.identifier.absfor | 110901 - Autonomic Nervous System | |
local.identifier.ariespublication | MigratedxPub12254 | |
local.type.status | Published Version | |
local.contributor.affiliation | Zhu, Hai-Lei, Kyusha University | |
local.contributor.affiliation | Hirst, George, College of Medicine, Biology and Environment, ANU | |
local.contributor.affiliation | Ito, Yushi, Kyusha University | |
local.contributor.affiliation | Teramoto, Noriyoshi, Kyusha University | |
local.description.embargo | 2037-12-31 | |
local.bibliographicCitation.startpage | 129 | |
local.bibliographicCitation.lastpage | 138 | |
local.identifier.doi | 10.1038/sj.bjp.0706295 | |
dc.date.updated | 2015-12-12T07:32:16Z | |
local.identifier.scopusID | 2-s2.0-30644462833 | |
Collections | ANU Research Publications |
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