DOCA-ENHANCED SITES OF VASOPRESSIN-STIMULATED CAMP FORMATION IN RAT CORTICAL COLLECTING TUBULE

被引：3

作者：

MCARDLE, S ^{[1
]}

FALLET, R ^{[1
]}

JEFFRIES, WB ^{[1
]}

PETTINGER, WA ^{[1
]}

机构：

[1] CREIGHTON UNIV, MED CTR,MIDWEST HYPERTENS RES CTR,DEPT MED, 601 N 30TH ST,STE 6730, OMAHA, NE 68131 USA

来源：

AMERICAN JOURNAL OF PHYSIOLOGY | 1992年 / 263卷 / 06期

关键词：

MINERALOCORTICOID HYPERTENSION; ADENYLYL CYCLASE; G-PROTEINS;

D O I：

10.1152/ajprenal.1992.263.6.F1093

中图分类号：

Q4 [生理学];

学科分类号：

071003 ;

摘要：

In deoxycorticosterone acetate (DOCA)-NaCl hypertension, the effects of vasopressin (VP) in the cortical collecting tubule (CCT) are exaggerated. These include both the biochemical effect of VP-stimulated adenosine 3'-5'-cyclic monophosphate (cAMP) formation in the CCT and physiological effects of VP-mediated sodium and water retention. In this study, we examined the mechanism of enhanced VP-stimulated cAMP formation in the CCT. We compared cAMP formation in response to activators (following in parentheses) of the VP receptor (VP), of the stimulatory guanine nucleotide binding (G(s)) protein [guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS); F-], and of the catalytic subunit of adenylyl cyclase (forskolin, Mn2+) between control and DOCA-NaCl-treated rats. The effects of VP and forskolin were enhanced in CCT of DOCA-NaCl-treated animals by 201 and 139%, respectively, compared with control animals. Other activators, Mn2+ (150%), F- (142%), and GTPgammaS (156%), also caused augmented cAMP formation in the CCT of DOCA-NaCl-treated rats. The DOCA-NaCl-induced increment in cAMP response to VP remained after pretreatment of the rats with pertussis toxin (171 and 169% increase in response in DOCA-NaCl and control rats, respectively), suggesting that altered inhibitory guanine nucleotide binding (G(i)) protein function is not the mechanism for the altered response to VP in the CCT. Further evidence that G(i) function is intact in DOCA-NaCl animals is that epinephrine (via alpha2-adrenoceptor stimulation) inhibited VP-stimulated cAMP accumulation to a similar degree in DOCA-NaCl and control rats (86 and 76%, respectively). In conclusion, the stimulated effects of both G(s) and the catalytic subunit of adenylyl cyclase are increased in the CCT of DOCA-NaCl-treated animals. The formation of cAMP through activation of each of the major components, the V2-Vasopressin receptor, the G(s) protein, and the catalytic unit, is exaggerated without altered function of G(i) protein. The mechanism by which all the components of this linkage is increased is unknown.

引用

页码：F1093 / F1097

页数：5