Regulation of adenylate cyclase type VIII splice variants by acute and chronic Gi/o-coupled receptor activation

Steiner, Debora; Avidor‐Reiss, Tomer; Schallmach, Ester; Butovsky, Elena; Lev, Nirit; Vogel, Zvi

doi:10.1042/bj20041670

Cited by 9 publications

(4 citation statements)

References 41 publications

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“…We found that Gi/o plays a role in the action potential-independent GABA release in CeA, as PTX pre-treatment reduced the mean frequencies of mIPSCs in the CeA neurons from morphine WD rats but had no effects in placebo rats. This concurs with studies in cultured cell lines showing opioid-induced adenylyl cyclase superactivation that was sensitive to PTX treatment, implicating the involvement of PTX-sensitive Gi/o proteins in mediating these adaptive responses (Tso and Wong, 2000 ; Steiner et al, 2005 ). Another possibility may include a PTX-pretreatment induced substitution of Gi/o by Gz.…”

Section: Discussionsupporting

confidence: 86%

Acute morphine alters GABAergic transmission in the central amygdala during naloxone-precipitated morphine withdrawal: role of cyclic AMP

Bajo

Madamba

Roberto

et al. 2014

Front. Integr. Neurosci.

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The central amygdala (CeA) plays an important role in opioid addiction. Therefore, we examined the effects of naloxone-precipitated morphine withdrawal (WD) on GABAergic transmission in rat CeA neurons using whole-cell recordings with naloxone in the bath. The basal frequency of miniature inhibitory postsynaptic currents (mIPSCs) increased in CeA neurons from WD compared to placebo rats. Acute morphine (10 μ M) had mixed effects (≥20% change from baseline) on mIPSCs in placebo and WD rats. In most CeA neurons (64%) from placebo rats, morphine significantly decreased mIPSC frequency and amplitude. In 32% of placebo neurons, morphine significantly increased mIPSC amplitudes but had no effect on mIPSC frequency. In WD rats, acute morphine significantly increased mIPSC frequency but had no effect on mIPSC amplitude in 41% of CeA neurons. In 45% of cells, acute morphine significantly decreased mIPSC frequency and amplitude. Pre-treatment with the cyclic AMP inhibitor (R)-adenosine, cyclic 3',5'-(hydrogenphosphorothioate) triethylammonium (RP), prevented acute morphine-induced potentiation of mIPSCs. Pre-treatment of slices with the Gi/o G-protein subunit inhibitor pertussis toxin (PTX) did not prevent the acute morphine-induced enhancement or inhibition of mIPSCs. PTX and RP decreased basal mIPSC frequencies and amplitudes only in WD rats. The results suggest that inhibition of GABAergic transmission in the CeA by acute morphine is mediated by PTX-insensitive mechanisms, although PTX-sensitive mechanisms cannot be ruled out for non-morphine responsive cells; by contrast, potentiation of GABAergic transmission is mediated by activated cAMP signaling that also mediates the increased basal GABAergic transmission in WD rats. Our data indicate that during the acute phase of WD, the CeA opioid and GABAergic systems undergo neuroadaptative changes conditioned by a previous chronic morphine exposure and dependence.

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Section: Discussionsupporting

confidence: 86%

Acute morphine alters GABAergic transmission in the central amygdala during naloxone-precipitated morphine withdrawal: role of cyclic AMP

Bajo

Madamba

Roberto

et al. 2014

Front. Integr. Neurosci.

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“…Acute exposure to agonists of G i/o -coupled receptors—such as MOR, m 4 (muscarinic type 4), D 2 (dopaminergic type 2), and CB 1 (cannabinoid type 1) receptors—inhibits the activity of AC types I, V, VI, and VIII, while stimulating the activity of AC types II, IV, and VII [ 25 , 52 ]. Furthermore, acute activation of G i/o -coupled receptors leads to inhibition of AC-VIII-A and -B, but not of the AC-VIII-C splice variant in COS-7 cells transfected with MOR [ 53 ]. It would be interesting to investigate whether the cells coexpressing MOR and ORL1 utilize the same mechanism to regulate AC activity as well.…”

Section: Discussionmentioning

confidence: 99%

Differential Pharmacological Actions of Methadone and Buprenorphine in Human Embryonic Kidney 293 Cells Coexpressing Human μ-Opioid and Opioid Receptor-Like 1 Receptors

et al. 2011

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Methadone and buprenorphine are used in maintenance therapy for heroin addicts. In this study, we compared their effects on adenylate cyclase (AC) activity in human embryonic kidney (HEK) 293 cells stably overexpressing human μ-opioid receptor (MOR) and nociceptin/opioid receptor-like 1 receptor (ORL1) simultaneously. After acute exposure, methadone inhibited AC activity; however, buprenorphine induced compromised AC inhibition. When naloxone was introduced after 30 min incubation with methadone, the AC activity was enhanced. This was not observed in the case of buprenorphine. Enhancement of the AC activity was more significant when the incubation lasted for 4 h, and prolonged exposure to buprenorphine elevated the AC activity as well. The removal of methadone and buprenorphine by washing also obtained similar AC superactivation as that revealed by naloxone challenge. The study demonstrated that methadone and buprenorphine exert initially different yet eventually convergent adaptive changes of AC activity in cells coexpressing human MOR and ORL1 receptors.

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“…The close correlation between down-regulation of G␤ and ACS in SH-SY5Y cells suggests a cause-and-effect relationship, although the precise mechanistic link remains to be determined. However, from a knowledge that AC1 and AC8 mRNA is present in neuroblastoma cells (Jang and Juhnn, 2001) and that AC1 (Nielsen et al, 1996) and perhaps AC8 (Steiner et al, 2005) are inhibited by G␤␥, one possible mechanism whereby morphine sensitizes adenylate cyclase could be by the removal of a direct G␤␥-mediated inhibitory constraint. Indeed, this hypothetical mechanism may apply to the other morphine-sensitizable AC isoforms as well, because scavengers of G␤␥ were reported previously to block morphineinduced sensitization of AC5 and AC6 (Avidor-Reiss et al, 1996;Rubenzik et al, 2001), two AC isoforms also known to be inhibited by G␤␥ (Bayewitch et al, 1998).…”

mentioning

confidence: 99%

Long-Term Morphine Treatment Enhances Proteasome-Dependent Degradation of Gβ in Human Neuroblastoma SH-SY5Y Cells: Correlation with Onset of Adenylate Cyclase Sensitization

Moulédous¹,

Neasta²,

Uttenweiler-Joseph³

et al. 2005

Mol Pharmacol

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The initial aim of this study was to identify protein changes associated with long-term morphine treatment in a recombinant human neuroblastoma SH-SY5Y clone (sc2) stably overexpressing the human -opioid (MOP) receptor. In MOP receptor-overexpressing sc2 cells, short-term morphine exposure was found to be much more potent and efficacious in inhibiting forskolin-elicited production of cAMP, and long-term morphine exposure was shown to induce a substantially higher degree of opiate dependence, as reflected by adenylate cyclase sensitization, than it did in wild-type neuroblastoma cells. Differential proteomic analysis of detergent-resistant membrane rafts isolated from untreated and chronically morphine-treated sc2 cells revealed long-term morphine exposure to have reliably induced a 30 to 40% decrease in the abundance of five proteins, subsequently identified by mass spectrometry as G protein subunits ␣i 2 , ␣i 3 , ␤ 1 , and ␤ 2 , and prohibitin. Quantitative Western blot analyses of whole-cell extracts showed that long-term morphine treatment-induced down-regulation of G␤ but not of the other proteins is highly correlated (r 2 ϭ 0.96) with sensitization of adenylate cyclase. Down-regulation of G␤ and adenylate cyclase sensitization elicited by long-term morphine treatment were suppressed in the presence of carbobenzoxy-L-leucyl-L-leucyl-L-norvalinal (MG-115) or lactacystin. Thus, sustained activation of the MOP receptor by morphine in sc2 cells seems to promote proteasomal degradation of G␤ to sensitize adenylate cyclase. Together, our data suggest that the long-term administration of opiates may elicit dependence by altering the neuronal balance of heterotrimeric G proteins and adenylate cyclases, with the ubiquitin-proteasome pathway playing a pivotal role.

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Regulation of adenylate cyclase type VIII splice variants by acute and chronic Gi/o-coupled receptor activation

Cited by 9 publications

References 41 publications

Acute morphine alters GABAergic transmission in the central amygdala during naloxone-precipitated morphine withdrawal: role of cyclic AMP

Acute morphine alters GABAergic transmission in the central amygdala during naloxone-precipitated morphine withdrawal: role of cyclic AMP

Differential Pharmacological Actions of Methadone and Buprenorphine in Human Embryonic Kidney 293 Cells Coexpressing Human μ-Opioid and Opioid Receptor-Like 1 Receptors

Long-Term Morphine Treatment Enhances Proteasome-Dependent Degradation of Gβ in Human Neuroblastoma SH-SY5Y Cells: Correlation with Onset of Adenylate Cyclase Sensitization

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