Effects of suplatast tosilate on acutely dissociated sensory and paratracheal ganglia neurons

Abstract

In this study, we investigated the effects of suplatast on acutely dissociated single neurons of sensory and paratracheal ganglia using a patch-clamp technique. Suplatast had little effect on various responses caused by capsaicin, acid, bradykinin, serotonin and adenosine 5'-triphosphate in rat sensory neurons. Suplatast, even at 10-3 M, also did not induce any current at various membrane potentials in rat and guinea pig paratracheal ganglia neurons. Further, acetylcholine- and bradykinin-induced depolarizations were not affected by suplatast. On the other hand, in rat paratracheal ganglia neurons, 10-5 M nicotine-induced current were inhibited by suplatast in a concentration-dependent manner with a 50% inhibitory concentration of 9.86x10-5 M. The effect was noncompetitive and voltage-dependent. Furthermore, the effect was use-independent and not affected by the pretreatment time of suplatast. The results suggested that suplatast may inhibit neurotransmission at the paratracheal ganglia via the inhibition of nicotinic current. Thus, suplatast may attenuate cough production through the improvement of pathological conditions of the lower airway via suppressed acetylcholine release from the postganglionic nerve terminal.

Direct Potentiation of Capsaicin Current by Histamine and Its Effect by Suplatast on Rat Trigeminal Ganglia Neurons

“…These results suggest that suplatast may not affect TRPV1 receptor functions. Together with our previous study [12], it is further suggested that suplatast may have no direct effect on the sensory neurons/fibers, at least the nociceptive neurons/fibers (C- and nociceptive Aδ-fibers).…”

“…However, the antitussive effect of suplatast does not appear to be due to the anti-allergic effect caused by Th2 cytokine inhibition. Recently, we found that in rat paratracheal ganglia neurons, suplatast inhibited postsynaptic nicotinic current, and in rat trigeminal ganglion (TG) neurons, suplatast had little effect on various responses caused by capsaicin, acid, bradykinin, serotonin, and adenosine 5’-triphosphate (ATP) [12]. Moreover, suplatast is known to inhibit histamine releases from the mast cells [13].…”

Sulfonium Ligands of the α7 nAChR

“…As noted previously, compound S6 is suplatast, a known compound with anti-inflammatory activity [ 19 ], which has shown silent agonist activity in our present study. It has been proposed that at least the antitussive activity of suplatast may be due to its ability to function as a channel blocker of ganglionic (α3β4) nAChR [ 29 ], preventing afferent impulses to muscles associated with cough. Note that, while Zhou et al reported channel block with 100 µM suplatast, we observed inhibition of α3β4 receptors with an IC 50 of only 4.5 µM, and our data are consistent with a non-competitive mechanism of inhibition (i.e., channel block) since S6 inhibition was not surmountable by increasing ACh concentration.…”