Native and detergent-solubilized membrane extracts from Drosophila heads contain binding sites for phenylalkylamine calcium channel blockers

Greenberg, Robert M.; Striessnig, Jörg; Koza, Astrid; Dévay, Piroska; Glossmann, Hartmut; Hall, Linda M.

doi:10.1016/0020-1790(89)90077-2

Cited by 18 publications

(35 citation statements)

References 33 publications

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“…[N-methyl-3H]-LU 49888 photolabels a 135 K polypeptide in Drosophila head membranes Greenberg et al, 1989;Pelzer et al, 1989) with a sedimentation coefficient of 12 S upon sucrose gradient centrifugation after solubilization with digitonin (Greenberg et al, 1989). The Drosophila melanogaster phenylalkylamine-sensitive Ca2 +-channel seems to be unique, as Ca2+-antagonists from other chemical classes (benzothiazepines e.g.…”

Section: Introductionmentioning

confidence: 99%

“…These sites are not coupled (as are mammalian L-type Ca2 +-channel phenylalkylamine receptors) to 1,4 dihydropyridine sites Greenberg et al, 1989) and can be specifically photolabelled by the arylazide phenylalkylamine [N-methyl-3H]-LU 49888 ((-)-5-[(3-azido-phenethyl)-[N-methyl-3H]methylamino-2-(3,4,5-trimethoxy-phenyl)-2 -isopropylvalero -nitrile)].…”

Section: Introductionmentioning

confidence: 99%

“…(+)-cis-diltiazem; 1,4 dihydropyridines e.g. nitrendipine) interacted only very weakly or not at all with the radiolabelled receptor Greenberg et al, 1989). DPI 201-106 (4-3(4-diphenyl-methyl-1-piperazinyl)-2-hydroxy-propoxy-1H-indole-2-carbonitrile) is a new cardiotonic agent (Scholtysik et al, 1985).…”

Section: Introductionmentioning

confidence: 99%

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Very high affinity interaction of DPI 201‐106 and BDF 8784 enantiomers with the phenylalkylamine‐sensitive Ca²⁺‐channel in Drosophila head membranes

Glossmann

Zech

Striessnig

et al. 1991

British J Pharmacology

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1 Piperazinylindoles BDF 8784), drugs known to act on voltage-dependent Na+-channels, bind with very high affinity to a Ca2+-channel-associated phenylalkylamine receptor in Drosophila melanogaster head membranes. These compounds and (+)-tetrandrine, a naturally occurring Ca2 +-antagonist, were the most selective inhibitors for phenylalkylamine-labelled Drosophila Ca2 +-channels compared to mammalian L-type Ca2 +-channels. 2 Replacement of the cyano group by a methyl group in ( + )-DPI 201-106 ((+)-BDF 8784) increases the IC50 value for inhibition of phenylalkylamine labelling of Drosophila Ca2+-channels from 0.29 to 2.1 nm but decreases the IC50 value for inhibition of phenylalkylamine labelling of mammalian skeletal muscle Ca2 +-channels from 3480 to 49 nm. 3 DPI 201-106 enantiomers completely block (at 0.1 M) phenylalkylamine photolabelling of a 136 K polypeptide in Drosophila head membranes whereas 10pM aconitine or lidocaine are without effect.4 Assessment of the Ca2+-antagonist effects of the substituted DPI 201-106 enantiomers in K+-depolarized taenia strips from guinea-pig caecum yielded pA2 values of 6.33 + 0.07 for (-)-BDF 8784 and 6.99 + 0.17 for (+)-BDF 8784, respectively. 5 Piperazinylindoles, previously believed to act nonspecifically on voltage-dependent mammalian L-type Ca2+-channels, therefore have stereoselectivity for a novel binding site and chemical selectivity unrelated to local anaesthetic activity. 6 It is proposed that a very high affinity piperazinylindole-selective site is coupled to the phenylalkylamine receptor of Drosophila Ca2+-channels. These sites are still present on mammalian L-type Ca2+-channels but have lower affinity and/or are less tightly coupled to phenylalkylamine receptors on the cl-subunit.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Very high affinity interaction of DPI 201‐106 and BDF 8784 enantiomers with the phenylalkylamine‐sensitive Ca²⁺‐channel in Drosophila head membranes

Glossmann

Zech

Striessnig

et al. 1991

British J Pharmacology

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“…However, these antibodies bound to the 165 kDa protein from rabbit skeletal muscle and to the 190 kDa protein from crayfish muscle. From all these experiments it is clear that a recepmelanogaster) [26,27]. An analysis of the species which tor/protein is present in crayfish muscle which can bind confirmed presence of the DHP receptor suggests that the dihydropyridine antagonist PN 200-110; this prothis receptor is mostly associated with the T-tubular tein is homological with the Ca*+ antagonist receptor system.…”

Section: -440kmentioning

confidence: 96%

Characterization of DHP binding protein in crayfish striated muscle

1990

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The dihydropyridine calcium channel blocker, [3H]PN 200‐110, binds specifically also to crayfish muscle membranes, though with a binding capacity smaller than that measured with rabbit or human skeletal muscle membranes. [3H]PN 200‐110 binding proteins from the crayfish T‐tubules were solubilized and purified on WGA Sepharose or extracted from gel. The purified protein has a molecular mass of approximately 190 kDa under nonreducing conditions and was able to transport calcium after reconstitution. Polyclonal antibodies against crayfish T‐tubules enriched with purified DHP‐binding protein were shown to bind to DHP‐binding protein from both the crayfish and the rabbit skeletal muscle, although not with the same intensity. Electron microscopy showed the presence of ovoid particles. Our results suggest that a voltage‐dependent calcium channel may be present in crayfish skeletal muscle, which is homological with the L‐type calcium channel in rabbit skeletal muscle.

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“…In arthropods different voltagegated calcium channels play a key role for muscle contraction: presynaptic channels control the release of excitatory transmitter (mainly glutamate) [lO,l l] at the neuromuscular junction, whereas calcium channels in the plasma membrane of muscle cells mediate the influx of calcium ions for contraction and participate in the propagation of the action potential [12]. The structural characterization of invertebrate calcium channels is rudimentary [13][14][15] and none of their subunits have yet been cloned.Here we report for the first time the cloning of an invertebrate calcium channel a,-subunit from Musea domestica larvae (designated Mdla,) that is preferentially expressed in body wall muscle. The evolutionary relationship of Mdla, compared to the so far cloned vertebrate calcium channels has been studied by calculating a phylogenetic tree.…”

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Insect calcium channels

et al. 1994

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The complete ammo acid sequence of an invertebrate calcium channel ~,-subunit from housefly (Musca domestrca) larvae (designated Mdla,) has been deduced by cDNA cloning and sequence analysis. Mdb, shares higher percent sequence identity with 1,4-dihydropy~dine (DHP)-sensitive L-type than with DHP-insensitive calcium channels. As shown by whole mount in situ hybridization and immunostaining Mdla, is predominantly expressed in the larval body wall musculature.Key words: Calcium channel; cDNA cloning; Hybridization (in situ); Body wall muscle; Phylogenetic tree I. Int~uctiouIntracellular free Ca'+ acts as a second messenger for a variety of physiological processes. In electrically excitable cells Ca2' entry is mediated by different types (L-, N-, P-and T-type) of voltage-activated calcium channels, which are distinguished in vertebrates by biophysical and pharmacological criteria (for a review see [I]). These channels exist as hetero-oligomeric complexes of several subunits (a,, a,-&, /I and y-subunits), which have been cloned and sequenced from various tissues 12-53. a,-Subunits form the channel pore and are structurally homologous to the channel-forming subunits of voltage-activated sodium and potassium channels. Phylogenetic analyses of a,-subunits from different types of vertebrate calcium channels suggest that they evolved from a common ancestor gene, which diverged into at least two main subfamilies [ 11. One subfamily, classified as L-type channels according to electrophysiological criteria [6], is sensitive to calcium channel drugs, like 1,4-dihydropyridines (DHP), phenylalkylamines (PAA) and benzothiazepines (reviewed in [7]). All other calcium channel *Corresponding author. Fax: (43) (512) 588 627.Abbreviations: DHP, dihydropyridine; DIG, digoxigenin-1 l-dUTP; Mdla,, Musca domestica larvae a,-subunit; PAA, phenylalkylamines; PCR, polymerase chain reaction; SDS, sodium dodecyl sulfate. types are not DHP-sensitive but can be distinguished by toxins (for review see [8]).Much less is known about the structure and pharmacological sensitivity of voltage-gated calcium channels in insects, which are separated from vertebrates by about 600 million years in evolution [9]. In arthropods different voltagegated calcium channels play a key role for muscle contraction: presynaptic channels control the release of excitatory transmitter (mainly glutamate) [lO,l l] at the neuromuscular junction, whereas calcium channels in the plasma membrane of muscle cells mediate the influx of calcium ions for contraction and participate in the propagation of the action potential [12]. The structural characterization of invertebrate calcium channels is rudimentary [13][14][15] and none of their subunits have yet been cloned.Here we report for the first time the cloning of an invertebrate calcium channel a,-subunit from Musea domestica larvae (designated Mdla,) that is preferentially expressed in body wall muscle. The evolutionary relationship of Mdla, compared to the so far cloned vertebrate calcium channels has been studied by...

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Native and detergent-solubilized membrane extracts from Drosophila heads contain binding sites for phenylalkylamine calcium channel blockers

Cited by 18 publications

References 33 publications

Very high affinity interaction of DPI 201‐106 and BDF 8784 enantiomers with the phenylalkylamine‐sensitive Ca²⁺‐channel in Drosophila head membranes

Very high affinity interaction of DPI 201‐106 and BDF 8784 enantiomers with the phenylalkylamine‐sensitive Ca²⁺‐channel in Drosophila head membranes

Characterization of DHP binding protein in crayfish striated muscle

Insect calcium channels

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Native and detergent-solubilized membrane extracts from Drosophila heads contain binding sites for phenylalkylamine calcium channel blockers

Cited by 18 publications

References 33 publications

Very high affinity interaction of DPI 201‐106 and BDF 8784 enantiomers with the phenylalkylamine‐sensitive Ca2+‐channel in Drosophila head membranes

Very high affinity interaction of DPI 201‐106 and BDF 8784 enantiomers with the phenylalkylamine‐sensitive Ca2+‐channel in Drosophila head membranes

Characterization of DHP binding protein in crayfish striated muscle

Insect calcium channels

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Very high affinity interaction of DPI 201‐106 and BDF 8784 enantiomers with the phenylalkylamine‐sensitive Ca²⁺‐channel in Drosophila head membranes

Very high affinity interaction of DPI 201‐106 and BDF 8784 enantiomers with the phenylalkylamine‐sensitive Ca²⁺‐channel in Drosophila head membranes