Cloning of rabbit α1b-adrenoceptor and pharmacological comparison of α1a-, α1b- and α1d-adrenoceptors in rabbit

Piao, Hailan; Taniguchi, Tadatsugu; Nakamura, Seigo; Zhu, Jun; Suzuki, Fumiko; Mikami, Daisuke; Muramatsu, Ikunobu

doi:10.1016/s0014-2999(00)00171-0

Cited by 28 publications

(36 citation statements)

References 28 publications

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“…The drug showing the highest affinity among tested drugs was NAN-190; its subnanomolar affinity is equal to that of a representative a1-adrenoceptor antagonist, prazosin (pKi = 9 -10) (4,25,26). Furthermore, the binding affinity of NAN-190 for a 1-adrenoceptor was not different from that (pKi = 9.2) reported for 5-HT receptors (27), indicating that this drug is an antagonist of not only the 5-HT receptor but also the a1-adrenoceptor.…”

Section: Discussionmentioning

confidence: 99%

Affinity of Serotonin Receptor Antagonists and Agonists to Recombinant and Native α1-Adrenoceptor Subtypes

Yoshio

Taniguchi

Itoh

et al. 2001

Japanese Journal of Pharmacology

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ABSTRACT-Binding affinities of serotonin (5-HT)-receptor antagonists and agonists at human recombinant a1-adrenoceptor subtypes (a 1a-, a1b-and a1d-subtypes) were examined and compared with the functional affinities obtained in rat caudal artery (a1A-subtype), dog carotid artery (a1B-subtype) and rat thoracic aorta (=1D-subtype). Most of the 5-HT-receptor antagonists and agonists tested showed relatively high affinity to three a 1-adrenoceptor subtypes. The highest affinity close to 1 nM was seen for in binding and functional studies. 5-Methylurapidil (5-HT1A agonist) and BMY7378 (5-HT1A agonist) showed, respectively, a 1a(a 1A)-or a1d(a1D)-subtype selectivity in both binding and functional affinities, but spiperone (5-HT2A antagonist) showed a1b-selectivity only in binding affinity. Functional affinity of ritanserin (5-HT2A antagonist) to the a1B-subtype was approximately 500-fold lower than that of affinity to the =1b-subtype. The present results show that many 5-HT-receptor antagonists and agonists have high affinity to a1-adrenoceptors, but suggest that there is deviation between their functional affinities and binding affinities for some drugs.Keywords: Serotonin receptor antagonist, Serotonin receptor agonist, a 1-Adrenoceptor, Selectivity a1-Adrenoceptors comprise a heterogeneous family (1 -3). Molecular biological studies have provided evidence for the existence of at least three genes encoding a1a-, a1b-and a1d-adrenoceptors (with lowercase letters) that correspond to the pharmacologically defined native a1A-, a1B-and a 1D-adrenoceptors (with uppercase letters) (4, 5). Pharmacological studies have revealed several subtypeselective agents: for example, 5-methylurapidil, KMD-3213, RS-17053 and nigludipine for the a1a-subtype (6 -9); spiperone for the a1b-subtype (10); and BMY7378 for the a1d-subtype (11, 12). Among them, 5-methylurapidil, spiperone and BMY7378 were originally categorized in serotonin (5-HT) receptor agonists and / or antagonists.Many 5-HT receptor antagonists have been developed and some of them are now clinically used as anticoagulants, antihypertensive drugs and antipsychotic drugs (13,14). Such therapeutic diversity of 5-HT antagonists may be related to their wide spectrum for not only 5-HT receptor family but also for heterogeneous receptors such as dopamine receptors and a1-adrenoceptors (15, 16).The present study was undertaken to examine the possible selectivity for a1-adrenoceptor subtypes of 5-HT receptor agonists and antagonists including clinically active antipsychotic drugs. The selectivity was evaluated with two parameters: binding affinity to recombinant human a 1a-, a1b-and a1d-adrenoceptors expressed in Chinese hamster ovary (CHO) cells and functional affinity to native a1A-(rat caudal artery) (17), a 1B-(dog carotid artery) (18,19) and a 1D-(rat thoracic aorta) (20) adrenoceptors. A good relationship was already reported for a 1-adrenoceptorselective drugs between the recombinant and native a1-adrenoceptors (7, 21). MATERIALS AND METHODS Membrane preparation and radiolig...

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Section: Discussionmentioning

confidence: 99%

Affinity of Serotonin Receptor Antagonists and Agonists to Recombinant and Native α1-Adrenoceptor Subtypes

Yoshio

Taniguchi

Itoh

et al. 2001

Japanese Journal of Pharmacology

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“…Our inability to detect the role of the a 1D -receptor may be explainable by the fact that no one has yet succeeded in demonstrating any a 1D -binding in the brain of either the rat (Yang et al, 1997), mouse (Yang et al, 1998), or rabbit (Piao et al, 2000) using the above antagonists as displacing agents. Therefore the a 1D -receptor responsible for behavioral activation must have some unique property such as a potential location in the peripheral nervous system which in some way communicates with the CNS.…”

Section: Role Of a 1 -Adrenoceptors In Behavioral Activitymentioning

confidence: 99%

Emerging Evidence for a Central Epinephrine-Innervated α1-Adrenergic System that Regulates Behavioral Activation and is Impaired in Depression

Stone

Yang

Rosengarten

et al. 2003

Neuropsychopharmacol

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Currently, most basic and clinical research on depression is focused on either central serotonergic, noradrenergic, or dopaminergic neurotransmission as affected by various etiological and predisposing factors. Recent evidence suggests that there is another system that consists of a subset of brain a 1B -adrenoceptors innervated primarily by brain epinephrine (EPI) that potentially modulates the above three monoamine systems in parallel and plays a critical role in depression. The present review covers the evidence for this system and includes findings that brain a 1 -adrenoceptors are instrumental in behavioral activation, are located near the major monoamine cell groups or target areas, receive EPI as their neurotransmitter, are impaired or inhibited in depressed patients or after stress in animal models, and are restored by a number of antidepressants. This 'EPI-a 1 system' may therefore represent a new target system for this disorder.

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“…However, direct binding studies showed that BMY 7378 inhibits 3 H-prazosin binding in the rabbit aorta with low affinity, presumably by binding to α 1A -and α 1B -adrenergic receptors. Moreover, relative level of expression of α 1D -adrenergic receptor mRNA in rabbit aorta is approximately 50 × lower than that of the α 1A -adrenergic receptor mRNA (Satoh et al 1998;Piao et al 2000). Negligible α 1D -adrenergic receptor function in aortic tonus regulation seems to be typical of rabbits, because administration of BMY 7378 blocked the α 1D -adrenergic receptor in the aorta of rats, leading to its dilatation (Goetz et al 1995).…”

Section: Discussionmentioning

confidence: 92%

Role of α1-adrenergic receptor subtypes in contractility of the rabbit abdominal aorta in vitro

et al. 2013

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Investigation of the effect of α 1 -adrenergic receptor subtypes on the contraction of the abdominal aorta will allow for more effective treatment of hypertension by use of selective antagonists. The aim of the study was to evaluate the participation of α 1 -adrenergic receptor subtypes in the contractility of the aortic smooth muscle cells in rabbits. The in vitro experiments were performed in isolated tissue preparations from 30 adult female New Zealand rabbits. The abdominal aortic sections were placed in organ bath chambers and contracted with increasing doses of non-selective α 1 -adrenergic receptor agonist phenylephrine without pre-incubation or after incubation in α 1 -adrenergic receptor subtype-selective or non-selective antagonists. Separate sections were incubated with increasing concentrations of antagonists. Phenylephrine caused maximal rise in arterial smooth muscle tone to 4.75 ± 0.47 mN. The most potent in blocking phenylephrine induced contraction was 5-metylurapidil (α 1A -adrenergic receptor antagonist) followed by phentolamine and prazosin (non-selective α 1 -adrenergic receptor antagonists); BMY 7378 (α 1D -adrenergic receptor antagonist), cyclazosin and L-765.314 (α 1B -adrenergic receptor antagonists) were less effective. All antagonists, except BMY 7378 elicited relaxation of nonprecontracted aorta in dose dependent manner. Our results indicate that postsynaptic α 1A receptors are the most potent in producing rabbit abdominal aorta contraction, while α 1B and α 1D subtypes are less effective.

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Cloning of rabbit α1b-adrenoceptor and pharmacological comparison of α1a-, α1b- and α1d-adrenoceptors in rabbit

Cited by 28 publications

References 28 publications

Affinity of Serotonin Receptor Antagonists and Agonists to Recombinant and Native α1-Adrenoceptor Subtypes

Affinity of Serotonin Receptor Antagonists and Agonists to Recombinant and Native α1-Adrenoceptor Subtypes

Emerging Evidence for a Central Epinephrine-Innervated α1-Adrenergic System that Regulates Behavioral Activation and is Impaired in Depression

Role of α1-adrenergic receptor subtypes in contractility of the rabbit abdominal aorta in vitro

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