.alpha.- and .beta.-Adrenoceptors: From the Gene to the Clinic. Part 1. Molecular Biology and Adrenoceptor Subclassification

Jp, Hieble; We, Bondinell; Rr, Ruffolo

doi:10.1021/jm00018a001

Cited by 193 publications

(104 citation statements)

References 68 publications

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“…43±49 The alpha-1 adrenergic receptors were classi®ed into alpha-1a (formerly alpha-1c), alpha-1b and alpha-1d (formerly alpha1a) based on cDNA sequences and agonist and antagonists binding characteristics. 46,50±51 Capital letters denote the pharmacological classi®cation and lower case letters denote the cloned receptor subtypes (Tables 1±3). Throughout this review we will adhere to this convention of classi®cation and nomenclature.…”

Section: Classi®cation Of Alpha-adrenergic Receptor Subtypes In Humanmentioning

confidence: 99%

“…Throughout this review we will adhere to this convention of classi®cation and nomenclature. Pharmacological and ligand binding studies with selective agonists and antagonists lead to classi®ca- 46,47). A summary of the selective agonists and antagonists for these three subtypes is shown in Table 2.…”

Section: Classi®cation Of Alpha-adrenergic Receptor Subtypes In Humanmentioning

confidence: 99%

“…15,31 Since high concentrations of antagonists were used in these studies, the selectivity of the antagonists for alpha-1 and alpha-2 adrenergic receptors is compromised at high drug concentrations due to lack of speci®city. 46,51,54 Therefore, the assignment of a speci®c functional activity to a speci®c receptor class or subclass based only on pharmacological analyses is suggestive, at best. Further, although yohimbine and rauwolscine (highly selective alpha-2 adrenergic receptor anta- Figure 4 Proposed molecular mechanism of action of alpha-1 adrenergic receptors in penile corpus cavernosum smooth muscle cells.…”

Section: Classi®cation Of Alpha-adrenergic Receptor Subtypes In Humanmentioning

confidence: 99%

“…Although phentolamine has been used as an intracavernosal and oral agent in treatment of erectile dysfunction (reviewed in refs 27, 67), a detailed analysis of its mechanism of action in erectile tissue was not reported. Several classes of alpha adrenergic blockers have been synthesized and screened for their potential usefulness in inhibiting receptor activity (reviewed in refs 46,51). Different alpha-adrenergic receptor blockers possess various structural determinants that confer selectivity, af®nity and ef®cacy ( Figure 7).…”

Section: Alpha Adrenergic Receptor Blockade In Erectile Dysfunctionmentioning

confidence: 99%

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Role of alpha adrenergic receptors in erectile function

et al. 2000

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Penile erection is a complex physiological process in which the regulation of penile hemodynamics depends on signal input from central and peripheral nervous systems, and on the balance and interplay between several local physiological mediators (neurotransmitters, vasoactive agents and endocrine factors). A role for the sympathetic nervous system in attaining or maintaining penile¯accidity and detumescence is well recognized. However, the exact mechanisms of alpha-adrenergic receptor mediated erectile function remain poorly de®ned. The objective of this review is to summarize data presented in the literature and from our laboratory on alpha-adrenergic receptors, and to discuss the conceptual framework by which the alphaadrenergic receptor pathway modulates penile corpus cavernosum smooth muscle contractility. We will integrate the current state of knowledge of penile erection into one framework encompassing the biochemical and physiological pathways responsible for trabecular smooth muscle relaxation (erection) and contraction (detumescence). We will focus our discussion on local control mechanisms of alpha-adrenergic receptors and explore the following topics: (1) functional activity of alpha-1 and alpha-2 adrenergic receptors in the physiology of human penile erection; (2) identi®cation, classi®cation and characterization of alpha-1 and alpha-2 adrenergic receptor subtypes in human penile erectile tissue; (3) molecular mechanism of action of alpha-1 and alpha-2 adrenergic receptors in human penile erectile tissue; (4) blockade of alpha-1 and alpha-2 adrenergic receptor action by selective and non-selective alpha-1 and alpha-2 adrenergic receptor antagonists (blockers); (5) physiologic (functional) antagonism of alpha-1 and alpha-2 adrenergic receptor activity by vasodilators mediating smooth muscle relaxation; and (6) key areas of consensus, as well as critical gaps in the existing scienti®c knowledge concerning the rationale and the potential use of alpha-blockers in erectile function.

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Section: Classi®cation Of Alpha-adrenergic Receptor Subtypes In Humanmentioning

confidence: 99%

Section: Classi®cation Of Alpha-adrenergic Receptor Subtypes In Humanmentioning

confidence: 99%

Section: Classi®cation Of Alpha-adrenergic Receptor Subtypes In Humanmentioning

confidence: 99%

Section: Alpha Adrenergic Receptor Blockade In Erectile Dysfunctionmentioning

confidence: 99%

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Role of alpha adrenergic receptors in erectile function

et al. 2000

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“…Sympathetic neurotransmission exerts its predominant e ects via the a and b classes of adrenergic receptors, which comprise ®ve major subtypes (a-1 and a-2, and b-1, b-2 and b-3) (Hieble et al, 1995). In the present study, we examined whether ocular sympathetic nerves may in¯uence choroidal vascular architecture by acting on either the a or b class of adrenergic receptor by chronically administering an a or b antagonist and using morphometric analysis to determine whether vascular remodelling similar to that seen after ocular sympathetic denervation occurred.…”

Section: Introductionmentioning

confidence: 99%

Role of adrenergic receptors in vascular remodelling of the rat choroid

Steinle

Smith²

2002

British J Pharmacology

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1 Choroidal blood vessels, located between the sclera and retina, constitute the principle source of blood¯ow to ocular structures. The choroid is innervated by vasoconstrictor sympathetic and vasodilator parasympathetic nerves. 2 We have shown previously that sympathetic denervation for 6 weeks leads to signi®cant increases in choroidal thickness, percentage of choroid occupied by vascular lumina, and numbers of choroidal venules, large arterioles and outer retinal capillaries. Sympathetic dea erentation produces similar increases, indicating that loss of sympathetic nerve activity is responsible for increased vascularity after sympathectomy. Thus, sympathetic neurotransmission normally may be important in suppressing vascular proliferation in the adult rodent eye. 3 The aim of the present study was to determine whether sympathetic nerves act by way of adrenergic receptors to maintain normal choroidal vascular integrity. 4 The a-adrenoceptor antagonist, phentolamine (1 mg kg 71 day 71 ), the b-receptor antagonist, propranolol (1 mg kg 71 day 71 ), or saline vehicle was infused for 3 weeks using subcutaneously implanted osmotic minipumps. 5 In phentolamine treated rats, no signi®cant changes were noted relative to saline infused controls. However, propranolol treatment resulted in increases in choroidal thickness, vascular luminal area, and numbers of large choroidal venules and both small and large arterioles, approximating the remodelling seen after chronic sympathectomy. 6 We conclude that sympathetic nerves play a role in maintaining normal choroidal vascular architecture through actions mediated primarily by b-adrenoceptors.

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