https://pharmrev.aspetjournals.org/content/pharmrev/46/2/121.full.pdf

International Union of Pharmacology nomenclature of adrenoceptors.

Identification of angiotensin II receptor subtypes

The total and regional peripheral resistance and capacitance of the vascular system is regulated by the sympathetic nervous system, which influences the vasculature mainly through changes in the release of catecholamines from both the sympathetic nerve terminals and the adrenal medulla. The knowledge of the targets for noradrenaline and adrenaline, the main endogenous catecholamines mediating that influence, has recently been greatly expanded. From two types of adrenoceptors (α and β), we have now nine subtypes (α 1A , α 1B , α 1D , α 2A/D , α 2B , α 2A/D , β 1 , β 2 , and β 3 ) and two other candidates (α 1L and β 4 ), which may be conformational states of α 1A and β 1 -adrenoceptors, respectively. The vascular endothelium is now known to be more than a pure anatomical entity, which smoothly contacts the blood and forms a passive barrier against plasma lipids. Instead, the endothelium is an important organ possessing at least five different adrenoceptor subtypes (α 2A/D , α 2C , β 1 , β 2 , and β 3 ), which either directly or through the release of nitric oxide actively participate in the regulation of the vascular tone. The availability of transgenic models has resulted in a stepwise progression toward the identification of the role of each adrenoceptor subtype in the regulation of blood pressure and fine-tuning of blood supply to the different organs: α 2A/D -adrenoceptors are involved in the central control of blood pressure; α 1 -(primarily) and α 2B -adrenoceptors (secondarily) contribute to the peripheral regulation of vascular tone; and α 2A/D - and α 2C -adrenoceptors modulate transmitter release. The increased knowledge on the involvement of vascular adrenoceptors in many diseases like Raynaud9s, scleroderma, several neurological degenerative diseases (familial amyloidotic polyneuropathy, Parkinson disease, multiple-system atrophy), some kinds of hypertension, etc., will contribute to new and better therapeutic approaches.

Vascular Adrenoceptors: An Update

Characterization of the selectivity, specificity and potency of medetomidine as an α2-adrenoceptor agonist



Certain neuroleptic drugs, such as spiperone and (+) butaclamol, can discriminate between two populations of [3H]5-hydroxytryptamine ([3H]5-HT) binding sites in rat brain. The butyrophenone neuroleptic spiperone shows the greatest selectivity for these two binding sites, having at least a 3000-fold difference between its dissociation constants (2-12 nM versus 35,000 nM) for the high- and low-affinity sites, respectively. Inhibition of [3H]5-HT binding by spiperone in rat frontal cortex and corpus striatum yields distinctly biphasic inhibition curves with Hill slopes significantly less than unity. Results from nonlinear regression analysis of these inhibition studies were consistent with a two-site model in each brain region. In the frontal cortex the high-affinity neuroleptic sites comprised about 60% of the total [3/H]5-HT binding sites whereas in the corpus striatum they accounted for only 20% of the sites. Furthermore, saturation studies of [3H]5-HT binding assayed in the absence or presence of 1 μM-spiperone (a concentration that completely blocks the high-affinity site while having minimal activity at the low-affinity site) reveal a parallel shift in the Scatchard plot with no change in the dissociation constant of [3H]5-HT, but a significant decrease (64% in frontal cortex or 28% in corpus striatum) in the number of specific binding sites. These observations are consistent with the existence of at least two populations of [3H]5-HT binding sites having a differential regional distribution in rat brain.

Spencer Berthelsen

Papers

A functional basis for classification of alpha-adrenergic receptors.