A possible role of tyrosine kinases in the regulation of muscarinic receptor-activated cation channels in guinea pig ileum.
We investigated the effects of inhibitors for tyrosine kinases and phosphatases on the muscarinic receptor-activated nonselective cationic current. With nystatin-perforated whole-cell recording, the tyrosine kinase inhibitor genistein (1 approximately 10 micrograms/ml) reduced the amplitude of currents evoked by iontophoretically applied acetylcholine in a dose-dependent manner, the maximum inhibition being to about 46% of the control. In contrast, daidzein (10 micrograms/ml), an inactive analog of genistein, exerted little effect. These effects were unchanged when the cationic current was activated by internal perfusion of GTP gamma S (50 microM) bypassing the muscarinic receptor. A potent phosphatase inhibitor, orthovanadate (30 approximately 100 microM), on the other hand, increased the GTP gamma S-induced cationic current. These results suggest that tyrosine phosphorylation may be essential to regulate the Ca mobilization associated with muscarinic receptor-operated nonselective cation channels.
Inoue
R
R
Department of Pharmacology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Waniishi
Y
Y
Yamada
K
K
Ito
Y
Y
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects; D005260:Female; D019833:Genistein; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006168:Guinea Pigs; D006706:Homeostasis; D007082:Ileum / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D007529:Isoflavones / Q000494:pharmacology; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000187:drug effects / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000502:physiology*; D014638:Vanadates / Q000494:pharmacology
D004968:Estrogens, Non-Steroidal; D007473:Ion Channels; D007529:Isoflavones; D011976:Receptors, Muscarinic; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D014638:Vanadates; C004742:daidzein; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D000109:Acetylcholine