Premium
Modulation of calcium channel currents by arachidonic acid in single smooth muscle cells from vas deferens of the guinea‐pig
Author(s) -
Nagano Norihiro,
Watanabe Minora
Publication year - 1995
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1995.tb16678.x
Subject(s) - gtp' , vas deferens , guanosine , chemistry , bapta , biophysics , arachidonic acid , patch clamp , endocrinology , intracellular , medicine , biochemistry , biology , receptor , enzyme
1 Effects of arachidonic acid (AA) on voltage‐dependent Ca channel currents were investigated by whole‐cell‐clamp methods in single smooth muscle cells freshly isolated from vas deferens of the guinea‐pig 2 Ca channel current was decreased by application of 1–30 μ m AA in a concentration‐dependent manner. When Ca 2+ or Ba 2+ was the charge carrier, Ca channel current ( I Ca or I Ba ) was reduced by AA to a similar extent (IC 50 = 10 and 6 μ m , respectively). Addition of 15 m M BAPTA to the pipette solution did not affect the reduction of I Ba by 10 μ m AA 3 The effect of AA on I Ba was not prevented by internal application of 1 m M nordihydroguaiaretic acid (NDGA) and 1 m M indomethacin (Indo). When the pipette solution contained 0.1 m M guanosine‐5′‐triphosphate (GTP), I Ba was decreased slightly but significantly by application of 30 (M prostaglandin (PGF 2α ) but not by PGE 2 . This effect of PGF 2α was irreversible or not observed when the pipette solution contained 0.3 m M guanosine‐5′‐(3‐thiotriphosphate) (GTPγS) or both GTP or guanosine‐5′‐0‐(2‐thiodiphosphate) (GDPβS), respectively 4 External application of 100 units ml −1 superoxide dismutase slightly but significantly attenuated the inhibition of I Ba by 1–30 μ m AA. Intracellular application of 1 m M GDPβS or 0.3 m M GTPγS did not significantly change the effect of AA. Intracellular application of 0.1 m M 1‐(5‐isoquinolinesulphonyl)‐2‐methylepiperazine (H‐7) also did not change the effect of AA 5 These results indicate that the decrease in Ca channel currents in vas deferens smooth muscle cells is mainly due to AA itself, as opposed to its metabolites. The effect of AA may be due to AA itself, as opposed to its metabolites. The effect of AA may be due to its direct action on Ca channels or membrane phospholipids, but may not be mediated by activation of GTP binding proteins or protein kinase C. The inhibition of Ca channel current by AA may be partly induced by superoxide radicals derived from AA oxidation. PGF 2α also reduces Ca channel currents but probably by a separate mechanism via activation of a GTP binding protein.