GABA_B receptors couple to G proteins G_o, G^∗_o and G·_i1 but not to G_i2

Abstract

We studied the selectivity of GABAB receptors for coupling to G proteins by testing the ability of various purified G proteins to increase GABA binding to N‐ethylmaleimide (NEM)‐treated membranes of bovine brain. The addition of Go, G∗ o or gi1 to NEM‐treated membranes increased GABA binding in a dose‐dependent manner. However, the addition of Gi2 did not elicit a marked increase in GABA binding. When α subunits of G proteins were mixed with various brain βγ subunit complexes composed of different γ subunits, and they were added to the NEM‐treated membranes, Gi2 with any βγ subunits hardly increased GABA binding. On the other hand, Go with any βγ subunits caused a marked increase, though Go with a small γ subunit was more effective than that with a large γ subunit. These data suggest that the selective coupling of the G proteins to GABAB receptors is determined by the α subunit.

Presynaptic and postsynaptic GABAB receptors of neocortical neurons of the rat in vitro: Differences in pharmacology and ionic mechanisms

“…Rather, it appears as if these presynaptic GABA B receptors modulate Ca 21 currents, as shown in various cell types (Deisz and Lux, 1985;Doroshenko and Neher, 1991;Scholz and Miller, 1991). A possible explanation for the difference in coupling of GABA B receptors to effector systems, between the present data and those by Misgeld et al (1989), may be the diversity of G-proteins associated with GABA B receptors (Morishita et al, 1990).…”

Voltage‐dependent calcium channel β‐subunits in combination with α1 subunits, have a GTPase activating effect to promote the hydrolysis of GTP by Gαo in rat frontal cortex

“…Preadsorption of the anti-G-protein antibodies with their respective immunising peptides (500/2g/ml, 1 h, 30°C) specifically prevented the inhibition of the GABABergic-stimulation of GTPase (21 + 2.1%, n = 6 and 22 + 3%, n = 7 stimulation of GTPase by (-)-baclofen was observed following pretreatment of the anti-G~ and anti-Go antibodies, respectively, with their immunising peptides). GABAa receptors have also been reported to couple to both Go and Gil in bovine brain [29]. However, it would appear that only the coupling of GABAB receptors via Go is involved in the inhibition of calcium channel currents [4,30].…”

Molecular Structure and Physiological Functions of GABABReceptors

“…Evidence for a coupling of GABA B receptors to G proteins came from the sensitivity of agonist affinity to GTP analogs (10,144). Studies using N-ethylmaleimide (NEM), islet activated protein (IAP), pertussis toxin, or antisense knock-down provided evidence that GABA B receptors predominantly couple to G i ␣-and G o ␣-type G proteins (9,59,122,223,228). It is now well established that presynaptic GABA B receptors repress Ca 2ϩ influx by inhibiting Ca 2ϩ channels in a membrane-delimited manner via the G␤␥ subunits (see sect.…”