Contractile hyperreactivity and alteration of PKC activity in gastric fundus smooth muscle of diabetic rats.
Contraction dose dependently induced in gastric smooth muscle of diabetic rats by Bay K 8644 in the presence of 20 mM KCl was about two times that induced in controls, and was inhibited more than 50% by 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7). Contraction was caused in diabetics but usually not in controls by 10(-5) M phorbol 12-myristate 13-acetate (PMA). In diabetics, this contraction was about 2.5 times that in controls. Protein kinase C (PKC) activity in the soluble fraction was depressed by H-7 or staurosporine, and depended on PMA concentration, but was greater in diabetics than in controls at any PMA concentration. PKC activity in the soluble fraction was inhibited by lower Ca2+ concentration, and was greater in diabetics than in controls. Affinity and density of binding sites of a Ca2+ channel antagonist ligand, [3H]PN200-110, were the same in plasma membrane-enriched fractions isolated from either controls or diabetic preparations. Thus, hyperreactivity in diabetic fundus may depend, in part, on alteration of PKC properties, but not on the density of Ca2+ channels.
Sakai
Y
Y
Second Department of Physiology, School of Medicine, Showa University, Tokyo, Japan.
Inazu
M
M
Shamoto
A
A
Zhu
B
B
Homma
I
I
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology* / Q000378:metabolism / Q000503:physiopathology*; D005748:Gastric Fundus / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology; D017275:Isradipine / Q000378:metabolism; D008297:Male; D009119:Muscle Contraction / Q000502:physiology; D009130:Muscle, Smooth / Q000201:enzymology* / Q000378:metabolism / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D015220:Calcium Channels; D007546:Isoquinolines; D010879:Piperazines; D011189:Potassium Chloride; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D000109:Acetylcholine; D013755:Tetradecanoylphorbol Acetate; D009638:Norepinephrine; D017275:Isradipine