Phosphoinositide-generated messengers in cardiac signal transduction.

A multitude of agonists like e.g. endothelin-1, angiotensin-II, serotonin, thrombin, histamine and vasopressin as well as alpha 1-adrenergic and muscarinic stimulation lead to stimulation of the phosphoinositide cycle in the heart. Besides the seven membrane spanning-domain receptor-coupled stimulation of the key enzyme of the phosphoinositide cycle, phospholipase C-beta, another class of hormones, growth factors, also couple to the phosphoinositide cycle, now through receptors with intrinsic tyrosine kinase activity that can phosphorylate and stimulate the phospholipase C-gamma isozyme. In this review we summarize the multitude of receptor (sub)types, G-protein-subunit- and phospholipase C-isozymes that are present in the heart. Furthermore, generation of second messengers and cellular responses are described together with the (patho)physiological implications for the heart of phosphoinositide cycle activation and second messenger accumulation.