Assignment of G-protein subtypes to specific receptors inducing inhibition of calcium currents

Kleuss, Christiane; Hescheler, Jürgen; Ewel, C.; Rosenthal, Walter; Schultz, Günter; Wittig, Burghardt

doi:10.1038/353043a0

Cited by 568 publications

(261 citation statements)

References 46 publications

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“…In this context, it is worth noting that a total of 800 di erent abgcon®gurations are theoretically possible and it is likely that some of these con®gurations de®ne the speci®city of G protein interactions. The ®ndings that the Gbgsubunit con®guration can confer speci®city to the signaling pathways regulated by Ga o also supports this view (Kleuss et al, 1991;Kleuss et al, 1992).…”

Section: Diversity Of G Protein Signalingmentioning

confidence: 68%

Regulation of cell proliferation by G proteins

Dhanasekaran

Tsim²,

Dermott³

et al. 1998

Oncogene

136

107

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G Proteins provide signal transduction mechanisms to seven transmembrane receptors. Recent studies have indicated that the a-subunits as well as the bg-subunits of these proteins regulate several critical signaling pathways involved in cell proliferation, di erentiation and apoptosis. Of the 17 a-subunits that have been cloned, at least ten of them have been shown to couple mitogenic signaling in ®broblast cells. Activating mutations in Ga s , Ga i2 , and Ga 12 have been correlated with di erent types of tumors. In addition, the ability of the bg-subunits to activate mitogenic pathways in di erent cell-types has been de®ned. The present review brie¯y summarizes the diverse and novel signaling pathways regulated by the a-as well as the bg-subunits of G proteins in regulating cell proliferation.

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Section: Diversity Of G Protein Signalingmentioning

confidence: 68%

Regulation of cell proliferation by G proteins

Dhanasekaran

Tsim²,

Dermott³

et al. 1998

Oncogene

136

107

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“…No such differences are known for the classical PTX-sensitive inhibitory G a subunits, G i a1-3 (Taussig and Gilman 1995;Sunahara et al 1996). These regulatory patterns indicate that the functional significance of heterogeneity at the level of inhibitory G proteins lies not exclusively in conferring specificity to receptor/G coupling (Kleuss et al 1991;Leaney et al 2000). Instead, they open the opportunity for the existence of multiple inhibitory AC pathways within a single cell.…”

Section: Discussionmentioning

confidence: 99%

“…Identification of the signal transduction pathway mediating tolerance/dependence is hampered by the ability of ORs to activate multiple inhibitory G proteins and intracellular effector systems (Gudermann et al 1992). Several experimental approaches have been employed to elucidate the specificity of signal transduction cascades in situ, such as application of site-directed anti-G protein antibodies (Simonds et al 1989), antisense strategies (Kleuss et al 1991), and over-expression of genetically modified PTXresistant inhibitory G a subunits (Leaney et al 2000). However, each of these approaches failed to define specific inhibitory AC signalling pathways most likely because of a pronounced functional redundancy between inhibitory G a subunits (Tang et al 1991;Sunahara et al 1996).…”

Section: Discussionmentioning

confidence: 99%

Identity of adenylyl cyclase isoform determines the G protein mediating chronic opioid‐induced adenylyl cyclase supersensitivity

Ammer¹,

Christ²

2002

Journal of Neurochemistry

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To determine the intracellular signal transduction pathway responsible for the development of tolerance/dependence, the ability of G z a to substitute for pertussis toxin (PTX)-sensitive G proteins in mediating adenylyl cyclase (AC) supersensitivity was examined in the presence of defined AC isoforms. In transiently l-opioid receptor (OR) transfected COS-7 cells (endogenous inhibitory G proteins: G i a2, G i a3 and G z a), neither acute (1 lmol/L) nor chronic morphine treatment (1 lmol/L; 18 h) influenced intracellular cAMP production. Coexpression of the l-OR together with AC type V and VI fully restored the ability of morphine to acutely inhibit cAMP generation. Chronic morphine treatment further resulted in the development of tolerance/dependence, as assessed by desensitization of the acute inhibitory opioid effect (tolerance) as well as the induction of AC supersensitivity after drug withdrawal (dependence). Specific direction of l-OR signalling via G z a by both PTX treatment and G z a over-expression had no effect on chronic morphine regulation of AC type V, but completely abolished the development of tolerance/dependence with AC type VI. Similar results were obtained in stably l-OR-expressing HEK293 cells transiently cotransfected with G z a and either AC type V or VI. Coprecipitation studies further verified that G z a specifically binds to AC type V but not type VI. Taken together, these results demonstrate that in principle each of the OR-activated G proteins per se is able to mediate AC supersensitivity. However, they also indicate that it is the molecular nature of AC isoform that selects and determines the OR-activated G protein mediating tolerance/dependence.

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“…Also, SOM-14 could hyperpolarize cortical neurons of the CNS. This is made possible by increasing K + current (Wang et al, 1989) and inhibiting a voltage-dependent Ca 2+ current via a GTP-binding protein (Dichter et al, 1990;Kleuss et al, 1991). It was found that SOM inhibited the GLU-evoked response, indicating its inhibitory action on the excitability of postsynaptic neuron.…”

Section: Discussionmentioning

confidence: 99%

Effects of Somatostatin on the Responses of Rostrally Projecting Spinal Dorsal Horn Neurons to Noxious Stimuli in Cats

Jung

Lee

et al. 2008

Korean J Physiol Pharmacol

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Somatostatin (SOM) is a widely distributed peptide in the central nervous system and exerts a variety of hormonal and neural actions. Although SOM is assumed to play an important role in spinal nociceptive processing, its exact function remains unclear. In fact, earlier pharmacological studies have provided results that support either a facilitatory or inhibitory role for SOM in nociception. In the current study, the effects of SOM were investigated using anesthetized cats. Specifically, the responses of rostrally projecting spinal dorsal horn neurons (RPSDH neurons) to different kinds of noxious stimuli (i.e., heat, mechanical and cold stimuli) and to the Aδ -and C-fiber activation of the sciatic nerve were studied. Iontophoretically applied SOM suppressed the responses of RPSDH neurons to noxious heat and mechanical stimuli as well as to C-fiber activation. Conversely, it enhanced these responses to noxious cold stimulus and Aδ -fiber activation. In addition, SOM suppressed glutamate-evoked activities of RPSDH neurons. The effects of SOM were blocked by the SOM receptor antagonist cyclo-SOM. These findings suggest that SOM has a dual effect on the activities of RPSDH neurons; that is, facilitation and inhibition, depending on the modality of pain signaled through them and its action site.

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Assignment of G-protein subtypes to specific receptors inducing inhibition of calcium currents

Cited by 568 publications

References 46 publications

Regulation of cell proliferation by G proteins

Regulation of cell proliferation by G proteins

Identity of adenylyl cyclase isoform determines the G protein mediating chronic opioid‐induced adenylyl cyclase supersensitivity

Effects of Somatostatin on the Responses of Rostrally Projecting Spinal Dorsal Horn Neurons to Noxious Stimuli in Cats

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