INCREASED EXPRESSION OF INHIBITORY GUANINE-NUCLEOTIDE-BINDING PROTEINS IN MEMBRANES FROM RENAL PROXIMAL TUBULES, BUT NOT BRAIN STRIATA, OF THE NORMOTENSIVE AND THE SPONTANEOUSLY HYPERTENSIVE RAT

Background Dysfunctional dopamine neurotransmission and defective D1(A ) receptor-G protein coupling exist in renal proximal tubules (RPT) of the spontaneously hypertensive rat (SHR). Objective To determine whet her differential expression of G proteins contributes to these anomalo us phenomena. Methods We examined the expression levels of the alpha-s ubunits of G proteins, in RPT of SHR and the normotensive Wistar-Kyoto (WKY) rat, as well as in striatal membranes, where dopamine functions and receptor-G protein coupling are known to be normal. Results In ge neral, rat striatal membranes displayed overall higher expression leve ls of the different alpha-subunits, relative to those of RPT membranes , Moreover, no significant differences were observed between G protein levels in rat striata in SHR and WKY rats. However, in RPT, both subu nits of G(s) alpha were equally expressed in SHR and WKY rats. G(11)al pha, was expressed in RPT of SHR and WKY rats to the same levels, but neither G(o) alpha nor G(z) alpha was detected in these membranes; hig her (50%) expression levels of G(i2)alpha were found in SHR. The large st difference in alpha-subunit expression levels between SHR and WKY R PT was observed for G(i3)alpha. This protein was present in SHR RPT at levels 4.8-fold higher than those in WKY rat RPT. The only alpha-subu nit which was slightly depressed (by 20%) in SHR was G(q) alpha. Concl usion The overexpression of G(i2)alpha and G(i3)alpha in SHR RPT may b e of importance in the genesis of hypertension in this animal.