Cj. Clark et al., GUANINE-NUCLEOTIDE REGULATORY PROTEIN ALTERATIONS IN YOUNG MILAN HYPERTENSIVE STRAIN RATS, Biochimica et biophysica acta. Molecular basis of disease, 1225(2), 1994, pp. 149-157
Vascular smooth muscle cell membranes from prehypertensive rats of the
Milan hypertensive strain (MHS) were used to examine adenylyl cyclase
activity and its regulation by guanine nucleotide regulatory proteins
(G-proteins). Basal adenylyl cyclase activity was similar in MHS and
Milan normotensive strain (MNS) membranes. Forskolin (10(-4) M) produc
ed a significantly greater stimulatory response in MHS membranes, but
this was not observed with NaF (10(-2) M). Isoproterenol (10(-4) M) ca
used a significantly decreased stimulation of adenylyl cyclase activit
y in MHS membranes, while prostaglandin E(1) (10(-5) M) produced simil
ar responses in the two strains. G(i) function and GTP responses, as o
bserved by biphasic effects of GTP on isoproterenol-stimulated membran
es, were similar in both strains. The levels of G(i)2 alpha and G(q) a
lpha/G(11)alpha were similar in the two strains, while the levels of G
(s) alpha (44 and 42 kDa forms) and the beta-subunit were significantl
y reduced by similar to 20% in MHS membranes. The alpha-subunit of G(i
)3 was dramatically reduced by similar to 80% in MHS membranes. The af
finities of beta-adrenergic receptors for the antagonist, cyanopindolo
l, were similar in the two strains; however, the number of beta-adreno
ceptors was substantially reduced in MHS membranes. These findings may
be of relevance to altered vascular reactivity and transmembrane ion
distribution observed in the MHS.