title: [I(KACh) inhibitor 2-[(4-methylphenyl)sulfonylcarbamido]-1-(4-nitrobenzyl)pyridinium bromide (2-AP27) is a muscarinic M(2) receptor antagonist].
abstract: Aminopyridines are known to inhibit acetylcholine-activated K(+) current (I(KACh)) in cardiac myocytes. The aim of this study was to examine the effect of 2-aminopyridine sulfonylcarbamide derivative 2-AP27 on isoprenaline-stimulated L-type Ca(2+) current (I(CaL)) and to identify whether 2-AP27 acts via blocking of muscarinic M(2)-receptors in frog cardiomyocytes. The whole-cell configuration of the patch-clamp technique was used to record I(CaL) in enzymatically isolated cardiac myocytes. Isoprenaline (0.1 microM), an agonist of beta(1)-beta(2)-adrenoreceptors, stimulated the I(CaL) up to 475+/-61% (n=4) (P<0.05) vs. control. Then, in the first series of experiments, carbachol (0.01 microM), an agonist of M(2 )muscarinic receptors, reduced the stimulatory effect of isoprenaline to 42+/-15% vs. isoprenaline alone. 2-AP27 (100 microM) alone completely abolished the inhibitory effect of carbachol on isoprenaline-stimulated I(CaL), which recovered to 95+/-5.8% of the effect of isoprenaline. In the second series of experiments, adenosine (1microM), an agonist of A(1)-adenosine receptors, reduced the stimulatory effect of isoprenaline on I(CaL) to 56+/-10% (n=3) (P<0.05). Then 2-AP27 (100 microM) applied in the presence of adenosine, had no effect on I(CaL), which remained at 51+/-7.9% (n=3) (P<0.05) of the effect of isoprenaline. These results suggest that 2-AP27, a new derivative of 2-AP, containing 4-toluolsulfonylcarbamide instead of amino group and quaternizated nitrogen by 4-nitrobenzylbromide in pyridine ring, is acting as an antagonist of muscarinic M(2) receptors in frog ventricular myocytes.
authors: Institute of Cardiology, Kaunas University of Medicine, Sukileliu 17, 50161 Kaunas.
authors: Vytenis Arvydas
authors: VA
authors: Skeberdis
authors: Vida
authors: V
authors: Gendviliene
authors: Danguole
authors: D
authors: Zablockaite
authors: Irma
authors: I
authors: Martisiene
authors: Antanas
authors: A
authors: Stankevicius
mesh_terms: D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D006168:Guinea Pigs; D007545:Isoproterenol / Q000494:pharmacology; D018727:Muscarinic Antagonists; D032383:Myocytes, Cardiac / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D011726:Pyridinium Compounds / Q000494:pharmacology*; D011898:Ranidae; D011976:Receptors, Muscarinic / Q000187:drug effects*; D013268:Stimulation, Chemical
chemical_list: D018727:Muscarinic Antagonists; D011726:Pyridinium Compounds; D011976:Receptors, Muscarinic; D002217:Carbachol; D000241:Adenosine; D007545:Isoproterenol