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(...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.展开更多
Let A be an abelian category and M∈A.Then M is called a(D_(4))-object if,whenever A and B are subobjects of M with M=A⊕B and f:A→B is an epimorphism,Ker f is a direct summand of A.In this paper we give several equi...Let A be an abelian category and M∈A.Then M is called a(D_(4))-object if,whenever A and B are subobjects of M with M=A⊕B and f:A→B is an epimorphism,Ker f is a direct summand of A.In this paper we give several equivalent conditions of(D_(4))-objects in an abelian category.Among other results,we prove that any object M in an abelian category A is(D_(4))if and only if for every subobject K of M such that K is the intersection K_(1)∩K_(2)of perspective direct summands K_(1)and K_(2)of M with M=K_(1)+K_(2),every morphismφ:M→M/K can be lifted to an endomorphismθ:M→M in End _(A)(M).展开更多
基金the National Key R&D Program of China(2018YFC1312700)the National Naturai Science Foundation of China(831730043)+4 种基金the Program of Innovative Research Team of the National Natural Science Foundation(81721001)Program for Changjiang Scholars and Innovative Research Team in University(IRT1216)Key Research and Development Projects of Science and Technology Innovation of Social and People's Livelihood in Chongqing City,(cstc2018jscx-mszdX0024)Clinical Medical Research Talent Training Program from The Third Military Medical University(2018XLCi012)National Institutes of Health,USA(P01HL074940,DK039308,and DK119652).
文摘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.
基金The Elementary Innovation Team Foundation supported by NORINCO Group in China(2021CXTD52)The Taishan Scholars Foundation supported by Shandong Provence in China。
文摘Let A be an abelian category and M∈A.Then M is called a(D_(4))-object if,whenever A and B are subobjects of M with M=A⊕B and f:A→B is an epimorphism,Ker f is a direct summand of A.In this paper we give several equivalent conditions of(D_(4))-objects in an abelian category.Among other results,we prove that any object M in an abelian category A is(D_(4))if and only if for every subobject K of M such that K is the intersection K_(1)∩K_(2)of perspective direct summands K_(1)and K_(2)of M with M=K_(1)+K_(2),every morphismφ:M→M/K can be lifted to an endomorphismθ:M→M in End _(A)(M).
