ABSTRACT
Since -adrenergic receptors are coupled to Gs(+) protein, their activation by either Epi or NE results in an increase in AC activity, cAMP generation, and subsequent activation of PKA (Part E). In contrast, postsynaptic 1-adrenergic receptors mediate their intracellular effects by activating membrane-bound PLC (also through a Gs(+) protein), which generates DG and IP3 as second messengers (Chs. 4 and 5). In turn, IP3 liberates Ca2+ from intracellular stores, and DG and Ca2+ activate membrane-bound PKC. In smooth muscle cells (e.g., arterioles), this intracellular mechanism is required for contraction. Cytoplasmic Ca2+ binds to calmodulin (CaM), calmodulin-dependent myosin light chain kinase (MLCK) is activated, myosin becomes phosphorylated, and increased myosin ATPase activity leads to contraction. Conversely, smooth muscle cells relax when intracellular cAMP levels rise (due to 2-adrenergic receptor stimulation), since activated PKA decreases MLCK activity, but increases that of MLC phosphatase (which dephosphorylates myosin). In cardiac myocytes, cAMP generation and subsequent PKA activation from 1-receptor stimulation leads to phosphorylation of Ca2+ L-channel proteins in plasma membranes, allowing extracellular Ca2+ to diffuse into cells in support of enhanced contractility. In SA and AV nodes of the heart, 1-receptor stimulation leads to increased Ca2+ conductance through both Ca2+ T and L channels, increasing rapidity of depolarization and heart rate (Ch. 19).
