Control of opiate receptor-adenylate cyclase interactions by calcium ions and guanosine-5′-triphosphate

Wilkening, Douglas; Sabol, Steven L.; Nirenberg, Marshall W.

doi:10.1016/0006-8993(80)90105-5

Cited by 17 publications

(5 citation statements)

References 17 publications

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“…In brain tissue the adenylate cyclase activity exhibits a biphasic response to Ca2+; low concentrations activate and higher concentrations inhibit the activity (Cheung et al, 1975;Brostrom et al, 1975;Lynch et al, 1977;Piascik et al, 1980). Similar results were observed with neuroblastoma glioma hybrid cells (Wilkening et al, 1980) and with at least one glioma cell line (Brostrom et al, 1976). This Ca2+ activation is mediated by the Ca2+-dependent regulator protein, calmodulin (Cheung, 1980).…”

Section: Pinchasi a N D D M Michaelsonsupporting

confidence: 81%

“…2. Since in various tissues low concentrations of Ca2+ activate the enzyme by a calmodulindependent mechanism and higher concentrations inhibit the enzyme (Brostrom et al, 1975;1976;Lynch et al, 1977;Cheung et al, 1980;Piascik et al, 1980;Wilkening et al, 1980), we specifically examined the effect of extremely low Ca2+ levels (10-8-10-7M) on the cyclase. The effect of Ca2+ was found to be monophasic, i.e., only inhibitory, in both the absence and the presence of calmodulin.…”

Section: Discussionmentioning

confidence: 99%

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Adenylate Cyclase of Torpedo Synaptosomes Is Inhibited by Calcium and Not Affected by Muscarinic Ligands

Pinchasi

Michaelson

1982

Journal of Neurochemistry

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Cholinergic synaptosomes isolated from the electric organ of Torpedo contain membrane-bound adenylate cyclase activity (approximately 6 pmol/mg protein/min), which is dependent on the presence of guanine nucleotides. The activity is strongly dependent on temperature and only slightly affected by NaCl. The Torpedo adenylate cyclase is completely inhibited by low levels of free Ca2+ (KD approximately 0.5 microM). This effect is not altered by either trifluoperazine or addition of exogenous calmodulin. Ca2+ has no effect on the activation step of the adenylate cyclase by guanyl-5'-yl imidodiphosphate (GppNHp), and Mn2+ abolishes the Ca2+-dependent inhibition of cyclic AMP synthesis. These findings suggest that Ca2+ exerts its effect by direct interaction with a site located on the catalytic subunit. Torpedo synaptosomes contain presynaptic inhibitory muscarinic receptors. The binding of muscarinic agonists to the receptors is modulated (to lower affinity) by GTP. However, muscarinic ligands, examined under a variety of assay conditions, have no effect on adenylate cyclase activity. These results suggest that although both the muscarinic receptor and the adenylate cyclase are coupled to G proteins, they either interact with different G proteins or are situated in different regions of the presynaptic membrane.

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Section: Pinchasi a N D D M Michaelsonsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Adenylate Cyclase of Torpedo Synaptosomes Is Inhibited by Calcium and Not Affected by Muscarinic Ligands

Pinchasi

Michaelson

1982

Journal of Neurochemistry

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“…Two main mechanisms have been proposed to explain the inhibition of adenylate cyclase activity by Ca2+: (1) a competitive inhibition of the formation of the substrate complex M&+-ATP (due to the formation of Ca2+ -ATP complex, Birnbaumer, 1973); (2) a desensitization of receptors coupled to this enzyme (Steer and Levitzki, 1975;Partington et al, 1980;Wilkening et al, 1980). The present data are compatible with these interpretations; the inhibition by Ca2+ of the basal adenylate cyclase activity in hippocampal membranes likely involved the…”

Section: Discussionmentioning

confidence: 99%

Ca²⁺‐Guanine Nucleotide Interactions in Brain Membranes. I. Modulation of Central 5‐Hydroxytryptamine Receptors in the Rat

Mallat

Hamon

1982

Journal of Neurochemistry

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The present study indicates that central 5‐hydroxytryptamine (5‐HT; serotonin) receptors can be modulated in opposite directions by Ca2+ and guanine nucleotides [guanosine triphosphate (GTP), β, γ‐imidoguanosine 5′‐triphosphate (GppNHp)]. Thus CaCl2 (≥0.5 mm) inhibited whereas GTP and GppNHp (10 μm) stimulated the 5‐HT‐sensitive adenylate cyclase in the hippocampus of newborn rats. Both the affinity (Kd−1) and the number (Bmax) of [3H]5‐HT binding sites in hippocampal membranes from adult rats were increased in the presence of Ca2+ (≥0.25 mm); GTP (≥0.1 mm) and GppNHp (≥0.3; μm) produced reverse effects. The efficacy of guanine nucleotides in inhibiting specific [3H]5‐HT binding was counteracted by Ca2+: the addition of this cation (5mm‐CaCl2) to the assay mixture resulted in a 40‐fold increase in the IC50 for GTP; the IC50 for GppNHp increased five‐fold under the same condition. The examination of the respective effects of Ca2+ and of GTP on the specific binding of [3H]5‐HT to various hippocampal membrane preparations (from developing rats, from subcellular fractions of adult tissues, and from adult rats after the selective degeneration of serotoninergic innervation in the forebrain) indicated that the amplitudes of the Ca2+‐induced increase and of the GTP‐induced decrease were generally correlated. This conclusion did not apply to striatal membranes of kainic acid‐treated rats because [3H]5‐HT binding sites persisting after the intrastriatal injection of kainic acid (i.e., half of the total number in striatal membranes from control rats) were markedly less affected by GTP but at least as responsive as control membranes to the Ca2+‐induced increase. These data are compatible with the hypothesis of a possible coupling of some–but not all–[3H]5‐HT binding sites to adenylate cyclase in the rat brain.

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“…The exact repertoire of AC isoenzymes in NG108-15 cells is not known. These cells were shown to contain a Ca 2+ -stimulated AC activity [18] and AC-VI, but not AC-I or -II [19]. It is thus possible that these cells contain the other Ca 2+ -stimulatable AC isoenzyme, namely AC-VIII.…”

Section: Introductionmentioning

confidence: 94%

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

Steiner

Avidor‐Reiss

Schallmach

et al. 2005

Biochemical Journal

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We previously reported that acute agonist activation of G(i/o)-coupled receptors inhibits adenylate cyclase (AC) type VIII activity, whereas agonist withdrawal following chronic activation of these receptors induces AC-VIII superactivation. Three splice variants of AC-VIII have been identified, which are called AC-VIII-A, -B and -C (with AC-VIII-B missing the glycosylation domain and AC-VIII-C lacking most of the C1b area). We report here that AC-VIII-A and -B, but not -C, are inhibited by acute mu-opioid and dopaminergic type D2 receptor activation, indicating that the C1b area of AC-VIII has an important role in AC inhibition by G(i/o)-coupled receptor activation. On the other hand the glycosylation sites in AC-VIII did not play a role in AC-VIII regulation. Although AC-VIII-A and -C differed in their capacity to be inhibited by acute agonist exposure, agonist withdrawal after prolonged treatment led to a similar superactivation of all three splice variants, with no significant change in AC-VIII expression. AC-VIII superactivation was not affected by pre-incubation with a cell permeable cAMP analogue, indicating that the superactivation does not depend on the agonist-induced reduction in cAMP levels. The superactivated AC-VIII-A, -B and -C were similarly re-inhibited by re-application of agonist (morphine or quinpirole), returning the activity to control levels. These results demonstrate marked differences in the agonist inhibition of the AC-VIII splice variants before, but not after, superactivation.

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Control of opiate receptor-adenylate cyclase interactions by calcium ions and guanosine-5′-triphosphate

Cited by 17 publications

References 17 publications

Adenylate Cyclase of Torpedo Synaptosomes Is Inhibited by Calcium and Not Affected by Muscarinic Ligands

Adenylate Cyclase of Torpedo Synaptosomes Is Inhibited by Calcium and Not Affected by Muscarinic Ligands

Ca²⁺‐Guanine Nucleotide Interactions in Brain Membranes. I. Modulation of Central 5‐Hydroxytryptamine Receptors in the Rat

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

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Control of opiate receptor-adenylate cyclase interactions by calcium ions and guanosine-5′-triphosphate

Cited by 17 publications

References 17 publications

Adenylate Cyclase of Torpedo Synaptosomes Is Inhibited by Calcium and Not Affected by Muscarinic Ligands

Adenylate Cyclase of Torpedo Synaptosomes Is Inhibited by Calcium and Not Affected by Muscarinic Ligands

Ca2+‐Guanine Nucleotide Interactions in Brain Membranes. I. Modulation of Central 5‐Hydroxytryptamine Receptors in the Rat

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

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Ca²⁺‐Guanine Nucleotide Interactions in Brain Membranes. I. Modulation of Central 5‐Hydroxytryptamine Receptors in the Rat