Alpha-1 and alpha-2 adrenoceptor binding in cerebral cortex: Competition studies with [3H]prazosin and [3H]idazoxan

Reader, Tomás A.; Brière, Richard; Grondin, Louise

doi:10.1007/bf01244641

Cited by 28 publications

(15 citation statements)

References 35 publications

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“…With the concentrations used in this study (10 −5 , 10 −4 ), there is no more selectivity of the drug. Our data are consistent with the affinity of α 1 adrenoceptors for idazoxan [25]; K D values of 609 n m for idazoxan and 5400 n m for phenylephrine respectively, but an α 1 population with high affinity for phenylephrine ( K D = 240) was also described [26]. Moreover, the affinity for α 2 adrenoceptors [25] is low for phenylephrine K D = 1900 n m ) in comparison with idazoxan ( K D = 2.3 n m ).…”

Section: Discussionsupporting

confidence: 90%

“…With the concentrations used in this study (10 )5 , 10 )4 ), there is no more selectivity of the drug. Our data are consistent with the affinity of a 1 adrenoceptors for idazoxan [25];…”

Section: R E S U L T Smentioning

confidence: 99%

“…K D values of 609 nM for idazoxan and 5400 nM for phenylephrine respectively, but an a 1 population with high affinity for phenylephrine (K D ¼ 240) was also described [26]. Moreover, the affinity for a 2 adrenoceptors [25] is low for phenylephrine K D ¼ 1900 nM) in comparison with idazoxan (K D ¼ 2.3 nM).…”

Section: R E S U L T Smentioning

confidence: 99%

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Idazoxan effects upon contractile activity in the rat aorta are related to α₁ adrenoceptors and L‐type channels

Şerban

Șerban

Nechifor

2004

Fundamemntal Clinical Pharma

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Idazoxan is an alpha(2) adrenoceptor antagonist and alpha(1)/alpha(2) partial agonist which also blocks imidazoline receptors. Although idazoxan is widely used in pharmacological studies, its intrinsic vasoactive properties could bring about some limitations. Others have shown that in rat aorta contracted by phenylephrine idazoxan induces relaxation and that in rat small arteries it preferentially antagonizes the alpha(1)-mediated response. We further investigated this matter, using the rat aorta and focusing on the endothelium-independent effects and on L-type channels. In our study, idazoxan inhibited the contraction induced by phenylephrine, an effect which was stronger in the presence of endothelium, but did not affect the contractions induced by various other agents (high potassium, angiotensin II, prostaglandin F(2alpha)). This preferential inhibition was attenuated by 10(-4) m, but not by 10(-5) m yohimbine, and also reduced by 10(-2) m tetraethylammonium and blunted by 10(-4) m methoxyverapamil. In concentrations above 10(-5) m idazoxan induced weak contractions of the de-endothelized rings, which were prazosin- and methoxyverapamil-sensitive. Others have suggested that cyclic guanosine monophospate mediates the idazoxan-induced endothelium-dependent relaxation, but this is difficult to reconcile with our findings. Potassium efflux could play some role in the direct relaxing effect of idazoxan. The observed idazoxan effects appear as based on action upon alpha(1) receptors, but a direct interaction with L-type calcium channels could also be taken into consideration.

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Section: Discussionsupporting

confidence: 90%

“…With the concentrations used in this study (10 )5 , 10 )4 ), there is no more selectivity of the drug. Our data are consistent with the affinity of a 1 adrenoceptors for idazoxan [25];…”

Section: R E S U L T Smentioning

confidence: 99%

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Idazoxan effects upon contractile activity in the rat aorta are related to α₁ adrenoceptors and L‐type channels

Şerban

Șerban

Nechifor

2004

Fundamemntal Clinical Pharma

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“…After thawing, the frozen sections were preincubated for 15 minutes in a sodium/potassium phosphate buffer, 50 mM at pH 7.40, for both ␣ 1 -and ␣ 2 -noradrenergic receptors (Diop et al, 1987;Reader et al, 1987) and in 0.17 mM Tris-HCl buffer (pH 7.4) for 5-HT 1A receptors (Radja et al, 1993a;Reader et al, 1995 receptors. In every experiment, sections from spinal-cordtransected cats were always incubated with sections from control animals, and control animal were sometimes used in more than one experiment.…”

Section: Ligand Binding Of Tissue Sectionsmentioning

confidence: 99%

Autoradiographic study of ?1- and ?2-noradrenergic and serotonin1A receptors in the spinal cord of normal and chronically transected cats

1999

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“…Reactions were carried out in 50 mM Tris-HCl (pH 7.4) at 25°C for 75 min. RX821002 (0.1 M) was used to define nonspecific binding (20,21).…”

Section: Receptor Binding Assaysmentioning

confidence: 99%

Isolation and Characterization of a Novel ConusPeptide with Apparent Antinociceptive Activity

McIntosh

Corpuz

Layer

et al. 2000

Journal of Biological Chemistry

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Cone snails are tropical marine mollusks that envenomate prey with a complex mixture of neuropharmacologically active compounds. We report the discovery and biochemical characterization of a structurally unique peptide isolated from the venom of Conus marmoreus. The new peptide, mr10a, potently increased withdrawal latency in a hot plate assay (a test of analgesia) at intrathecal doses that do not produce motor impairment as measured by rotarod test. The sequence of mr10a is NGVCCGYKLCHOC, where O is 4-trans-hydroxyproline. This sequence is highly divergent from all other known conotoxins. Analysis of a cDNA clone encoding the toxin, however, indicates that it is a member of the recently described T-superfamily. Total chemical synthesis of the three possible disulfide arrangements of mr10a was achieved, and elution studies indicate that the native form has a disulfide connectivity of Cys1-Cys4 and Cys2-Cys3. This disulfide linkage is unprecedented among conotoxins and defines a new family of Conus peptides.Conus is a genus of predatory marine gastropods that envenomate their prey. Prey capture is accomplished through a sophisticated arsenal of peptides that target specific ion channel and receptor subtypes. Each Conus venom appears to contain a unique set of 50 -200 peptides. The structure and function of only a small minority of these peptides have been determined to date. For peptides where function has been determined, three classes of targets have been elucidated: voltage-gated ion channels, ligand-gated ion channels, and G-protein-linked receptors.Conus peptides that target voltage-gated ion channels include those that delay the inactivation of sodium channels as well as blockers specific for sodium channels, calcium channels, and potassium channels. Peptides that target ligand-gated ion channels include antagonists of N-methyl-D-aspartate and serotonin receptors as well as competitive and non-competitive nicotinic receptor antagonists. Peptides that act on G protein receptors include neurotensin and vasopressin receptor agonists. The unprecedented targeting selectivity of conotoxins derives from specific disulfide bond frameworks combined with hypervariable amino acids within disulfide loops (see Ref. 1 for review). Due to the high potency and exquisite selectivity of the conopeptides, several are in various stages of clinical development for treatment of human disorders (2).In this report we describe the isolation of a new peptide from the venom of the marble cone, Conus marmoreus. C. marmoreus is found in the Indo-Pacific, from India to the Marshall Islands and Fiji. It preys upon various gastropods including other cone snails (3). We previously reported the isolation and characterization of a peptide from this venom that potently inhibits voltage-gated sodium channels (4). In this report, we describe the isolation of a novel peptide that appears antinociceptive and likely represents a defining member of a new family of Conus peptides. EXPERIMENTAL PROCEDURES Materials and HPLC 1 ConditionsThe venom of C...

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Alpha-1 and alpha-2 adrenoceptor binding in cerebral cortex: Competition studies with [3H]prazosin and [3H]idazoxan

Cited by 28 publications

References 35 publications

Idazoxan effects upon contractile activity in the rat aorta are related to α₁ adrenoceptors and L‐type channels

Idazoxan effects upon contractile activity in the rat aorta are related to α₁ adrenoceptors and L‐type channels

Autoradiographic study of ?1- and ?2-noradrenergic and serotonin1A receptors in the spinal cord of normal and chronically transected cats

Isolation and Characterization of a Novel ConusPeptide with Apparent Antinociceptive Activity

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Alpha-1 and alpha-2 adrenoceptor binding in cerebral cortex: Competition studies with [3H]prazosin and [3H]idazoxan

Cited by 28 publications

References 35 publications

Idazoxan effects upon contractile activity in the rat aorta are related to α1 adrenoceptors and L‐type channels

Idazoxan effects upon contractile activity in the rat aorta are related to α1 adrenoceptors and L‐type channels

Autoradiographic study of ?1- and ?2-noradrenergic and serotonin1A receptors in the spinal cord of normal and chronically transected cats

Isolation and Characterization of a Novel ConusPeptide with Apparent Antinociceptive Activity

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Product

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Idazoxan effects upon contractile activity in the rat aorta are related to α₁ adrenoceptors and L‐type channels

Idazoxan effects upon contractile activity in the rat aorta are related to α₁ adrenoceptors and L‐type channels