Cardiac alphai-adrenergic receptor stimulation: Positive inotropism and arrhythmias (part 2)

Positive inotropism and arrhythmias (part 2)

Molecular cloning studies suggest that there are three or four alpha1-adrenergic receptors subtypes, whereas radioligand binding and functional studies suggest that at least two pharmacologically distinct subtypes may be linked to different second messenger systems (reviewed in 3,4). These two alpha1-adrenergic receptors have been previously classified as alphaiA and alphaiB based on their affinity for the competitive antagonist WB 4101 (N-[2-(2,6-di-methoxyphenoxy) ethyl]-2,3 dihydro-1,4-benzedioxin-2 methanamine) and their sensitivity to the irreversible antagonist chloroethylclonidine. The relative amount of these subtypes varies with different species but not with development, during which their number decreases after birth.

The relationship between cloned and native subtypes is uncertain. Current opinion favours the view that the cloned alpha1A-adrenergic receptor corresponds to the pharmacologically defined alpham-adrenergic receptor, and that the cloned and pharmacologically defined alpha1B are identical. It is also postulated that the cloned alpha1C-adrenergic receptor cDNA encodes the pharmacologically defined alpha1A-subtype. Moreover, each subtype may show several isoforms. Three isoforms of alpha1C are generated by alternative splicing; they show similar ligand binding properties, at least in alpha1C-1 isoform cDNA-transfected COS cells. The alpha1C-1 isoform is largely expressed in human heart, as well as in liver and cerebellum . Most alpha1-adrenergic receptor subtypes stimulate the hydrolysis of inositol-containing phospholipids via interaction with pertussis toxin-insensitive G proteins of the Gq/Gn family, with subsequent activation of phospholipase C-beta activity; some alpha1-adrenergic receptors are coupled to the Gi-proteins. It’s time for you to start saving some money: you just need to visit the pharmacy that offers finest quality yasmin birth buy here with delivery straight to your door and all the confidentiality guarantees you ever need.