Effect of Yizhitongxuan decoction on learning and memory ability,Gαq/11 expression and Na^+-K^+-ATP enzyme activity in rat models of Alzheimer's Disease

OBJECTIVE: To study the effects of Yizhitongxuan decoction on learning and memory abilities, Gαq/11expression and Na+-K+-ATPenzymeactivityin rat models of Alzheimer's disease(AD) caused by injecting Aβ25-35 into the hippocampus.METHODS: Ninety male Wistar rats(age ≥10 months)were selected and injected with Aβ25-35 into their hippocampi to establish model animals,which were randomly divided into six groups including a sham-operated group(blank group), a model group, a donepezil HCL group(Western Medicinegroup),and ahigh/general/dilute concentrations of Yizhitongxuan decoction groups(TCMⅠⅡⅢgroup).The Morris watermaze was used to examine the learning and memory abilities of rats in each group by place navigation and spatial probe tests.Then, the rats were sacrificed to collect the hippocampi for biochemical tests, using western blotting to detect the expression of Gαq/11 and an ultramicro Na+-K+-ATP enzyme kit to measure Na+-K+-ATP enzyme activity.RESULTS:Yizhitongxuan decoction improved model rats' learning and memory abilities, and increased the expression of Gαq/11 in the hippocampus and the level of Na+-K+-ATP enzyme activity in braintissue.CONCLUSION: Yizhitongxuan decoction could improve model rats' learning and memory abilities,and had a regulating effect on the expression of Gαq/11and Na+-K+-ATP enzyme activity.

Effect of D_(4)Dopamine Receptor on Na^(+)-K^(+)-ATPase Activity in Renal Proximal Tubule Cells

Objective:Dopamine,via its receptors,plays a vital role in the maintenance of blood pressure by modulating renal sodium transport.However,the role of the D_(4)dopamine receptor(D_(4)receptor)in renal proximal tubules(PRTs)is still unclear.This study aimed to verify the hypothesis that activation of D_(4)receptor directly inhibits the activity of the Na+-K+-ATPase(NKA)in RPT cells.Methods:NKA activity,nitric oxide(NO)and cyclic guanosine monophosphate(cGMP)levels were measured in RPT cells treated with the D_(4)receptor agonist PD168077 and/or the D_(4)receptor antagonist L745870,the NO synthase inhibitor NG-nitro-L-arginine-methyl ester(L-NAME)or the soluble guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one(ODQ).Total D_(4)receptor expression and its expression in the plasma membrane were investigated by immunoblotting in RPT cells from Wistar-Kyoto(WKY)rats and spontaneously hypertensive rats(SHRs).Results:Activation of D_(4)receptors with PD168077,inhibited NKA activity in RPT cells from WKY rats in a concentration-and time-dependent manner.The inhibitory effect of PD168077 on NKA activity was prevented by the addition of the D_(4)receptor antagonist L745870,which by itself had no effect.The NO synthase inhibitor L-NAME and the soluble guanylyl cyclase inhibitor ODQ,which by themselves had no effect on NKA activity,eliminated the inhibitory effect of PD168077 on NKA activity.Activation of D_(4)receptors also increased NO levels in the culture medium and cGMP levels in RPT cells.However,the inhibitory effect of D_(4)receptors on NKA activity was absent in RPT cells from SHRs,which could be related to decreased plasma membrane expression of D_(4)receptors in SHR RPT cells.Conclusions:Activation of D_(4)receptors directly inhibits NKA activity via the NO/cGMP signaling pathway in RPT cells from WKY rats but not SHRs.Aberrant regulation of NKA activity in RPT cells may be involved in the pathogenesis of hypertension.