Characterization of α1-and α2-Adrenergic Receptors

Bylund, David B.; U’Prichard, David C.

doi:10.1016/s0074-7742(08)60225-1

Cited by 233 publications

(72 citation statements)

References 250 publications

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“…The outstanding feature of the isomeric ratios was the large ratio for each form of synephrine at x,-adrenoceptors particularly m-synephrine with a ratio of 420. This was greater than that for NA or for the equivalent octopamine, suggesting that when the configuration of There is considerable evidence that the cerebral and peripheral subtypes of cx-adrenoceptors are similar (Bylund & U'Prichard, 1983). However, caution is necessary in extrapolating too far, particularly as a2-adrenoceptor isotypes have been proposed to explain the pharmacological differences between rodent and non-rodent species (Cheung et al, 1982;Latifpour et al, 1982;Feller & Bylund, 1984;Alabaster et al, 1986) and there is mounting evidence of a heterogeneity within species (Bylund, 1985 Considering the members of a series of compounds, if the difference between pD2 and affinity remains constant as the pD2 falls, then loss of activity can be attributed entirely to loss of affinity.…”

Section: Discussionmentioning

confidence: 88%

Activities of octopamine and synephrine stereoisomers on α‐adrenoceptors

Brown¹,

McGrath

Midgley

et al. 1988

British J Pharmacology

100

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1 The activities of the (-)-and (+ )-forms of m-and p-octopamine and m-and p-synephrine on a,-adrenoceptors from rat aorta and anococcygeus and a2-adrenoceptors from rabbit saphenous vein were compared with those of noradrenaline (NA).2 The rank order of potency of the (-)-forms on cx,-adrenoceptors from rat aorta and a2-adrenoceptors was NA > m-octopamine = m-synephrine > p-octopamine = p-synephrine. The two m-compounds were 6 fold less active than NA on x,-adrenoceptors from rat aorta and 150 fold less active on x,-adrenoceptors. The two p-compounds were 1,000 fold less active than NA on both oqadrenoceptors from rat aorta and x2-adrenoceptors. The rank order ofpotency ofthe (-)-forms on oqadrenoceptors from rat anococcygeus was NA = m-synephrine > m-octopamine >p-octopamine = p-synephrine. m-Octopamine was 4 fold less active than NA and (-)-m-synephrine. The two pcompounds were 30 fold less active than NA. 3 The rank order of potency of the (+)-forms was NA>m-octopamine>m-synephrine>p-octopamine >p-synephrine on both a,-and M2-adrenoceptors. The potency ofeach ( + )-form was 1-2 orders of magnitude less than that of the (-) counterpart, the differences being greater for the stereoisomers of synephrine than for those of octopamine on both a,-and M2-adrenoceptors. 4 The yohimbine diastereoisomer antagonists, rauwolscine and corynanthine, were tested against (-)-NA and (-)-m-octopamine-induced contractions in both preparations. Based upon the known selectivities of these isomers for a-adrenoceptor subtypes, it is concluded that the rat aorta contains only a,-adrenoceptors while the rabbit saphenous vein possesses predominantly M2-adrenoceptors.5 Ligand binding data for the octopamine and synephrine stereoisomers at oq-and a2-binding sites from rat cerebral cortex was also obtained. (-)-Forms were more active than (+ )-forms. The rank order of affinity of the (-)-forms for both a,-and M2-binding sites was NA > m-octopamine = msynephrine >p-synephrine >p-octopamine. The relative affinities ofthe members ofthe series against a,-binding sites were very similar to their relative functional activities on rat aorta. However, the affinities of both m-and p-compounds relative to that of ( -)-NA were much greater at the x2-binding sites than were the relative activities in rabbit saphenous vein, possibly suggesting low intrinsic efficacy. Functional antagonist responses to NA by the (-)-octopamine and synephrines could not, however, be demonstrated on rat aorta or rabbit saphenous vein. 6 The activities of m-octopamine and m-synephrine were not significantly different from each other on either a,-adrenoceptors from rat aorta or x2-adrenoceptors; however, m-synephrine is more active than m-octopamine on a,-adrenoceptors from rat anococcygeus. Both m-octopamine and msynephrine can be considered to be naturally occurring x,-selective amines. However, if m-and poctopamine are co-released with NA in amounts proportional to their concentration, it is concluded that their activities on m,-and x2-adrenoceptors are too low to be ...

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Section: Discussionmentioning

confidence: 88%

Activities of octopamine and synephrine stereoisomers on α‐adrenoceptors

Brown¹,

McGrath

Midgley

et al. 1988

British J Pharmacology

100

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“…The range of densities ofa2-adrenoceptor binding sites in the rat cortex reported in the literature is wide (90-242fmolmg-1 protein, Bylund & U'Prichard, 1983;Lane et al, 1983), a finding probably related to different assay conditions and to membrane preparations being purified to different extents. In order to compare the binding of [3H] [3H]-idazoxan (1-12nM) to membranes from rat cerebrum was rapid, reversible, saturable and of high affinity.…”

Section: Resultsmentioning

confidence: 99%

“…However, the low affinity exhibited by yohimbine for truly 'high' affinity [3H]-prazosin (0.01-0.05 nM) sites suggests that [3H]-yohimbine binding is not to an a1-adrenoceptor site. This also means that the affinity ratio between yohimbine and prazosin is not as useful for differentiating between al-and a2-adrenoceptor subtypes as originally suggested (Bylund & U'Prichard, 1983). A moderately high potency of prazosin at rat a2-adrenoceptors has also been demonstrated in functional studies of noradrenaline release in the rat submandibular gland (Turner et al, 1984).…”

Section: Introductionmentioning

confidence: 95%

α₂‐Adrenoceptor subtypes and imidazoline‐like binding sites in the rat brain

Brown

MacKinnon

McGrath

et al. 1990

British J Pharmacology

117

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3 The affinities of 8-OH-DPAT, RU 24969 and methysergide determined against [3H]-idazoxan binding to the cortex and hippocampus correlate significantly with the binding site displaying low affinity for prazosin and previously designated a2A. In contrast, a poor correlation exists for the high affinity site for prazosin designated a2B* 4 [3H]-idazoxan, in the presence of 3Mm yohimbine, labels a site that displays high affinity towards cirazoline, naphazoline and guanabenz, but low affinity towards clonidine, p-aminoclonidine, adrenaline, noradrenaline and the a2-adrenoceptor antagonists yohimbine, rauwolscine, WY 26703 and BDF 6143.5 The results of this study indicate that [3H]-yohimbine labels two sites; the a2A-and a2B-adrenoceptors whereas [3H]-idazoxan labels an a2-adrenoceptor with a profile consistent with the CX2A-adrenoceptor subtype. In addition, [3H]-idazoxan labels an imidazoline binding site in the rat cortex that is pharmacologically distinct from a2-adrenoceptors. The low affinity of clonidine and p-aminoclonidine indicates that the imidazoline-like binding site in rat cortex is different from the site labelled by [3H]-clonidine and [3H]-p-aminoclonidine in human, rat and bovine brain stem, providing evidence of potential heterogeneity within this class of binding sites.

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“…Membranes were filtered, washed, dried, and counted as for muscarine re ceptors. The Kd for prazosin has been reported to be 0.14-0.31 nM for brain and 0.1-0.9 nM for peripheral tissues (Bylund and U'Prichard, 1983), so 3 nM [3Hlprazosin should label at least 75% of all known aj receptors. Nonspecific binding for vessel preparations was 30-50% of total binding.…”

Section: Assay Of Lycreceptorsmentioning

confidence: 99%

“…Filters were then washed, dried, and counted as for muscarine receptors. The Kd for this ligand is 1-3 nM (Bylund and U'Prichard, 1983), so 3 nM should yield at least 50% saturation. Nonspecific binding was 40-60% of total binding.…”

Section: Assay Of Lyrreceptorsmentioning

confidence: 99%

α-Adrenoreceptors and Muscarine Receptors in Human Pial Arteries and Micro Vessels: A Receptor Binding Study

Ferrari-Dileo

Potter

1985

J Cereb Blood Flow Metab

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Summary: Human pial arteries and intraparenchymal microvessels were isolated for enzyme assays and radio ligand binding studies of receptors, Special attention was paid to contamination with brain tissue, which was as sessed by luxol staining and cerebroside assays for myelin and by scanning electron microscopy, The amount of contamination was �1% for pial vessels and 14% for microvessel preparations, Significant levels of

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Characterization of α1-and α2-Adrenergic Receptors

Cited by 233 publications

References 250 publications

Activities of octopamine and synephrine stereoisomers on α‐adrenoceptors

Activities of octopamine and synephrine stereoisomers on α‐adrenoceptors

α₂‐Adrenoceptor subtypes and imidazoline‐like binding sites in the rat brain

α-Adrenoreceptors and Muscarine Receptors in Human Pial Arteries and Micro Vessels: A Receptor Binding Study

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Characterization of α1-and α2-Adrenergic Receptors

Cited by 233 publications

References 250 publications

Activities of octopamine and synephrine stereoisomers on α‐adrenoceptors

Activities of octopamine and synephrine stereoisomers on α‐adrenoceptors

α2‐Adrenoceptor subtypes and imidazoline‐like binding sites in the rat brain

α-Adrenoreceptors and Muscarine Receptors in Human Pial Arteries and Micro Vessels: A Receptor Binding Study

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α₂‐Adrenoceptor subtypes and imidazoline‐like binding sites in the rat brain