Guanine nucleotide binding proteins may modulate gating of calcium channels in vascular smooth muscle. II. Studies with guanosine 5'-(gamma)triphosphate.
Our previous studies with fluoride have indicated that G-proteins may mediate the gating of Ca++ channels in vascular smooth muscle (VSM). We now present further studies on the relationship between G-proteins and Ca++ channels in VSM using guanosine-5'-(gamma-thio)triphosphate (GTP gamma S), a hydrolysis-resistant analog of GTP. Rat tail artery helical strips pretreated with GTP gamma S in a cytosol-like solution contracted in a Ca++-dependent manner in the absence of a depolarizing concentration of K+, hormones or any other Ca++ agonists. Contraction was dependent on the concentrations of applied GTP gamma S. The ability of strips pretreated with GTP gamma S to contract in response to Ca++ was not reversed by repeated washing. Incubation with 1 mM GTP applied extracellularly did not induce tension development. Treatment with a subthreshold concentration of GTP gamma S shifted the K+ concentration-related tension curve to the left but did not alter the maximum response. The contractions induced by GTP gamma S pretreatment and by submaximal (60 mM) KCI were additive at all levels of Ca++ tested. Extra tension development could be evoked from tissue maximally contracted with GTP gamma S by adding maximal K+ and norepinephrine. The relaxing sensitivity of the GTP gamma S-related contraction to reversal by nifedipine was between those for K+ depolarization and norepinephrine, and the GTP gamma S-induced rise in tension was partially inhibited by the Ca++ channel blocker nifedipine. Ca++-elicited contraction of the GTP gamma S-pretreated strips was relaxed by forskolin, an adenylate cyclase activator, 3-isobutyl-l-methyl-xanthanine, a cyclic nucleotide phosphodiesterase inhibitor, and dibutyryl cyclic AMP.(ABSTRACT TRUNCATED AT 250 WORDS)
Zeng
Y Y
YY
Department of Physiology, University of Alberta, Edmonton, Canada.
Benishin
C G
CG
Pang
P K
PK
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000502:physiology; D003994:Bucladesine / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D005576:Colforsin / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013873:Thionucleotides / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects
D015220:Calcium Channels; D013873:Thionucleotides; D005576:Colforsin; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D003994:Bucladesine; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D019204:GTP-Binding Proteins; D009543:Nifedipine; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine; D009638:Norepinephrine