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

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. Furthermore, 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 9.86 × 10−5 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.

Short-term diabetic hyperglycemia suppresses celiac ganglia neurotransmission, thereby impairing sympathetically mediated glucagon responses

Short-term hyperglycemia suppresses superior cervical ganglia neurotransmission. If this ganglionic dysfunction also occurs in the islet sympathetic pathway, sympathetically mediated glucagon responses could be impaired. Our objectives were 1) to test for a suppressive effect of 7 days of streptozotocin (STZ) diabetes on celiac ganglia (CG) activation and on neurotransmitter and glucagon responses to preganglionic nerve stimulation, 2) to isolate the defect in the islet sympathetic pathway to the CG itself, and 3) to test for a protective effect of the WLDSmutation. We injected saline or nicotine in nondiabetic and STZ-diabetic rats and measured fos mRNA levels in whole CG. We electrically stimulated the preganglionic or postganglionic nerve trunk of the CG in nondiabetic and STZ-diabetic rats and measured portal venous norepinephrine and glucagon responses. We repeated the nicotine and preganglionic nerve stimulation studies in nondiabetic and STZ-diabetic WLDSrats. In STZ-diabetic rats, the CG fos response to nicotine was suppressed, and the norepinephrine and glucagon responses to preganglionic nerve stimulation were impaired. In contrast, the norepinephrine and glucagon responses to postganglionic nerve stimulation were normal. The CG fos response to nicotine, and the norepinephrine and glucagon responses to preganglionic nerve stimulation, were normal in STZ-diabetic WLDSrats. In conclusion, short-term hyperglycemia's suppressive effect on nicotinic acetylcholine receptors of the CG impairs sympathetically mediated glucagon responses. WLDSrats are protected from this dysfunction. The implication is that this CG dysfunction may contribute to the impaired glucagon response to insulin-induced hypoglycemia seen early in type 1 diabetes.