Differentiation of Receptor Systems activated by Sympathomimetic Amines

β-adrenoceptor blocker treatment and the cardiac β-adrenoceptor-G-protein(s)-adenylyl cyclase system in chronic heart failure

“…Noradrenaline, the primary signaling molecule of cardiac adrenergic activity, is a rather β-1 AR selective agonist (Lands et al 1967). In several animal studies, and also in humans, it has been shown that chronic activation of cardiac β-1 AR produces a cardiomyopathic phenotype; similar effects are observed with overexpression of β-1 AR in the heart of transgenic animals (for references, see Port and Bristow 2001;Lohse et al 2003;Hata et al 2004).…”

“…The subclassification of adrenoceptors (AR) into the subtypes α and β was initially introduced into the pharmacology of the sympathetic nervous system in 1948 by Ahlquist (1948) to explain the differences in action of noradrenaline and adrenaline. With the development of new and more specific drugs, it rapidly became apparent that both α-and β-AR can be subdivided into at least two subtypes: α-AR in the subtypes α-1 and α-2 (Langer 1974;Starke 1977), β-AR into the subtypes β-1 and β-2 (Lands et al 1967). In the last 10 years, with the introduction of molecular biology techniques into pharmacology, further AR subtypes have been introduced.…”

Current and prospective pharmacological targets in relation to antimigraine action

“…In 1967, two subtypes of the β-adrenoceptor were identified by comparing the rank orders of agonist potency (Ahlquist 1967;Lands et al 1967). The β 1 -adrenoceptor, the dominant receptor in heart and adipose tissue, was equally sensitive to noradrenaline and adrenaline, whereas the β 2 -adrenoceptor, responsible for relaxation of vascular, uterine, and airway smooth muscle, was much less sensitive to noradrenaline in comparison with adrenaline (Lands et al 1967).…”

“…The β 1 -adrenoceptor, the dominant receptor in heart and adipose tissue, was equally sensitive to noradrenaline and adrenaline, whereas the β 2 -adrenoceptor, responsible for relaxation of vascular, uterine, and airway smooth muscle, was much less sensitive to noradrenaline in comparison with adrenaline (Lands et al 1967). Highly selective antagonists for both β 1 -and β 2 -adrenoceptors have been developed, as well as many potent and selective β 2 -adrenoceptor agonists.…”

Using guinea pigs in studies relevant to asthma and COPD

“…Many fundamental processes, mediators and regulators of airways disease pathogenesis were discovered or demonstrated first in guinea pigs, including the Schultz-Dale (immediate type hypersensitivity) reaction, the actions of histamine, the cysteinyl-leukotrienes and their two receptors, beta adrenoceptor subtypes, thromboxane, vascular endothelial growth factor (VEGF), eotaxin, alveolar macrophage derived neutrophil chemotactic factor(s) (leukotriene B 4 and/or IL-8) and the roles of cAMP and inositol triphosphate in signal transduction [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19]. Receptor pharmacology in guinea pigs more closely matches that of human receptor pharmacology than most other commonly used species [1,20,21] (Table 1, Figs.…”