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 D1A receptor-G protein coupling exist in renal proximal tubules (RPT) of the spontaneously hypertensive rat (SHR).

OBJECTIVE

To determine whether differential expression of G proteins contributes to these anomalous phenomena.

METHODS

We examined the expression levels of the alpha-subunits 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 general, rat striatal membranes displayed overall higher expression levels 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 subunits of Gs alpha were equally expressed in SHR and WKY rats. Gi1 alpha was expressed in RPT of SHR and WKY rats to the same levels, but neither G(o) alpha nor Gz alpha was detected in these membranes; higher (50%) expression levels of Gi2 alpha were found in SHR. The largest difference in alpha-subunit expression levels between SHR and WKY RPT was observed for Gi3 alpha. This protein was present in SHR RPT at levels 4.8-fold higher than those in WKY rat RPT. The only alpha-subunit which was slightly depressed (by 20%) in SHR was Gq alpha.

CONCLUSION

The overexpression of Gi2 alpha and Gi3 alpha in SHR RPT may be of importance in the genesis of hypertension in this animal.