Pertussis toxin blocks melatonin-induced inhibition of forskolin-stimulated adenylate cyclase activity in the chick brain

Lp, Niles; M, Ye; Ds, Pickering; Sw, Ying

doi:10.1016/0006-291x(91)90177-9

Cited by 23 publications

(15 citation statements)

References 15 publications

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“…Thus, melatonin and its analogs inhibit dopamine-stimulated CAMP accumulation by activating melatonin receptors similar to those described pre- viously using other functional or binding assays. Furthermore, the inhibitory effect of melatonin on dopamine-stimulated CAMP accumulation was blocked by pretreatment with pertussis toxin, which also attenuates the inhibition by melatonin of forskolin-stimulated CAMP accumulation in retinal cells (Iuvone and Gan, 1994), brain (Niles et al, 1991), and pars tuberalis (Morgan et al, 1990). Thus, we suggest that melatonin stimulates receptors located on neurons that also contain Dl dopamine receptors, and that the melatonin receptors activate a G,-like guanyl nucleotide binding protein that inhibits the effect of G, activation by Dl dopamine receptor stimulation.…”

Section: Discussionmentioning

confidence: 99%

“…Occupation of melatonin receptors in retinal membranes inhibits forskolin-stimulated adenylate cyclase (Niles et al, 1991). We recently reported that cultured neural cells prepared from chick embryo retina have 2-iodomelatonin binding sites, and that occupation of melatonin receptors in these cultures inhibits forskolin-stimulated CAMP accumulation (Iuvone and Gan, 1994a).…”

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confidence: 99%

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Functional interaction of melatonin receptors and D1 dopamine receptors in cultured chick retinal neurons

Iuvone

Gan

1995

J. Neurosci.

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The possible interaction of melatonin receptors and D1 dopamine receptors was investigated in neural cells prepared from embryonic day 8 chick retinas and cultured for 6 d. Dopamine stimulated cAMP accumulation in cultured retinal cells. This effect of dopamine was antagonized by addition of dopamine receptor antagonists (haloperidol and SCH23390) or melatonin receptor agonists (melatonin, 2- iodomelatonin, and 6-chloromelatonin). The inhibition of dopamine- stimulated cAMP accumulation by melatonin was concentration dependent, with half-maximal inhibition at approximately 160 pM. Melatonin inhibited the effect of dopamine at all dopamine concentrations, suppressing the maximal response to the neurotransmitter by approximately 70%. Melatonin also inhibited the stimulation of cAMP accumulation by SKF 82958, a selective D1 dopamine receptor agonist. Pretreatment of cultures with pertussis toxin had no significant effect on dopamine-stimulated cAMP accumulation, but inhibited the response to melatonin. In contrast to its effect on cAMP accumulation, melatonin had no effect on dopamine-stimulated inositol phosphate accumulation. These results suggest that melatonin receptors are coupled to dopamine receptor-regulated adenylate cyclase via an inhibitory G protein, and demonstrate another mechanism, in addition to inhibition of dopamine release, through which melatonin can modulate dopaminergic neurotransmission.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Functional interaction of melatonin receptors and D1 dopamine receptors in cultured chick retinal neurons

Iuvone

Gan

1995

J. Neurosci.

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“…Melatonin has been shown to inhibit AC activity via a highaffinity receptor in vertebrate brain which is coupled to a pertussis toxin-sensitive G-protein (Niles et al, 1991;Ying et al, 1992). However, it should be emphasized that the inhibition of striatal AC activity, by melatonin and 2-iodomelatonin, does not involve the high-affinity Gi-coupled receptor for melatonin.…”

Section: Discussionmentioning

confidence: 99%

“…Pertussis toxin experiments were carried out as we have previously described (Niles et al, 1991) with some modifications. Fresh rat striatal tissue was placed into culture dishes containing 2 ml of a-minimum essential medium in 10 mM HEPES (pH 7.4 at 37°C) supplemented with 1% foetal bovine serum.…”

Section: Pertussis Toxin Treatmentmentioning

confidence: 99%

PK 11195 blockade of benzodiazepine‐induced inhibition of forskolin‐stimulated adenylate cyclase activity in the striatum

Tenn

Neu

Niles

1996

British J Pharmacology

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1 The effects of benzodiazepine receptor antagonists on the inhibition of forskolin-stimulated adenylate cyclase (AC) activity by various benzodiazepine (BZ) and indoleamine agonists in the rat striatum were investigated. 2 A biphasic inhibition of forskolin-stimulated AC activity by the peripheral-type agonist, Ro5-4864, and a multiphasic inhibition by the non-selective BZ, diazepam, was observed. One phase of AC inhibition is consistent with a Gi-coupled receptor-mediated action, whereas the other phases appear to involve a direct effect on the enzyme itself. 3 While the central-type antagonist, flumazenil, had no effect on the ability of Ro5-4864 to inhibit AC activity, the peripheral-type receptor ligand, PK 11195, abolished the first phase of inhibition. 4 PK 11195 and pertussis toxin were found to block the inhibitory effect of various BZs and the indoleamines, melatonin and 2-iodomelatonin, on induced AC activity. 5 Saturation binding studies, conducted at 30'C with [3H]-diazepam revealed a single binding site in the rat striatum (KD = 19.3 + 0.80 nM) which significantly decreased in affinity in the presence of GTP (KD = 30.5+2.6 nM; P<0.05). No significant change in B,,,, was observed. 6 These findings indicate the presence of G,-coupled BZ receptors in the rat striatum. Thus, suppression of cyclic AMP production may contribute to the diverse neuropharmacological effects of BZs, melatonin and related drugs.

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“…This receptor exists in interconverti ble high-and low-affinity states and it is sensi tive to guanine nucleotides and cations indi cating its coupling to a G protein [4]. It is now evident that this G protein is sensitive to per tussis toxin and mediates the inhibition of adenylate cyclase activity by melatonin [5].…”

Section: Introductionmentioning

confidence: 99%

Heparin Inhibits Melatonin Binding and Signal Transduction in Chick Brain

Niles

Harjivan²,

Nanji³

1994

Biological Signals

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The high-affinity receptor for melatonin is coupled to a pertussis toxin-sensitive, inhibitory guanine nucleotide regulatory protein, G_i, which mediates inhibition of adenylate cyclase activity in the chick and other species. Heparin has been found to uncouple α₂-adrenoceptors from a similar G_i;therefore it was of interest to examine the effect of this agent on melatonin binding and signal transduction in chick brain. In competition studies, melatonin inhibited the binding of 2-[¹²⁵I]iodomela-tonin with high- and low-affinities of K_H = 20 pM and K_L = 15 nM, respectively. In the presence of heparin (100 units/ml), a single site with an affinity of about 6 nM was detected. The monovalent cations, Na⁺ and Li⁺, produced a greater right-ward shift of the agonist competition curve than heparin and converted all high-affinity sites to a low affinity of ∼15–18 nM. In saturation studies, heparin reduced the affinity of high-affinity sites and caused a significant decrease in the density of low-affinity sites. In keeping with its ability to reduce high-affinity binding, heparin blocked melatonin''s inhibitory effect on forskolin-stimulated adenylate cyclase activity in chick brain synaptosomal membranes. These findings indicate that heparin impairs the coupling between the melatonin receptor and G_i, with a consequent decrease in binding affinity and a loss of receptor-mediated signalling.

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Pertussis toxin blocks melatonin-induced inhibition of forskolin-stimulated adenylate cyclase activity in the chick brain

Cited by 23 publications

References 15 publications

Functional interaction of melatonin receptors and D1 dopamine receptors in cultured chick retinal neurons

Functional interaction of melatonin receptors and D1 dopamine receptors in cultured chick retinal neurons

PK 11195 blockade of benzodiazepine‐induced inhibition of forskolin‐stimulated adenylate cyclase activity in the striatum

Heparin Inhibits Melatonin Binding and Signal Transduction in Chick Brain

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