Methoctramine and gallamine inhibit PI hydrolysis in guinea-pig gallbladder.
The present study aimed to determine the effect of two M2/M4-selective muscarinic receptor antagonists on blocking the hydrolysis of carbachol (CCh) stimulated phospho-inositide (PI) breakdown in order to address the possibility that a muscarinic receptor other than the M(3) receptor is involved in PI hydrolysis in this tissue. Gallbladder tissue slices labeled with myo-[2-3H] inositol were incubated with increasing concentrations of antagonists and agonist. After the reactions were terminated by the addition of chloroform/methanol, labeled inositol phosphates were separated using anion exchange chromatography. Muscarinic M2 antagonists methoctramine and gallamine both inhibited carbachol-induced PI breakdown at high concentrations, with log IC50 values of -5.145 and -6.049, respectively. Gallamine at 10(-5)M concentration failed to displace the dose-response curve for carbachol-induced accumulation of inositol triphosphate (IP3). Our data suggest that M(3) receptors play a major role in stimulation of PI hydrolysis in the guinea-pig gallbladder.
Cabadak
Hulya
H
Department of Biophysics, Marmara University School of Medicine, Tibbiye Caddesi No 49, Haydarpasa, 34668, Istanbul, Turkey. hcabadak@yahoo.com
Kan
Beki
B
D000818:Animals; D002217:Carbachol / Q000037:antagonists & inhibitors / Q000494:pharmacology; D003864:Depression, Chemical; D003959:Diamines / Q000494:pharmacology*; D005260:Female; D005703:Gallamine Triethiodide / Q000494:pharmacology*; D005704:Gallbladder / Q000187:drug effects / Q000378:metabolism*; D006168:Guinea Pigs; D006868:Hydrolysis; D066298:In Vitro Techniques; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000378:metabolism*; D043585:Receptor, Muscarinic M2 / Q000187:drug effects; D043588:Receptor, Muscarinic M4 / Q000187:drug effects
D003959:Diamines; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D010716:Phosphatidylinositols; D043585:Receptor, Muscarinic M2; D043588:Receptor, Muscarinic M4; D002217:Carbachol; C054938:methoctramine; D005703:Gallamine Triethiodide