depending on cell type: a) Gs alpha subunit-Gβγ complexes which release Gs that then stimulates adenyl cyclase to raise intracellular levels of cAMP and thereby activate cAMP-regulated protein kinases A-dependent cell signaling pathways (see PKA); b) Gq alpha subunit-Gβγ complexes which release Gq that then stimulates other cell signaling pathways (e.g. phospholipase C/IP3/cell Ca2+ mobilization/diacylglycerol/protein kinase Cs, calmodulin-modulated myosin light chain kinase, RAF/MEK/Mitogen-activated protein kinases, PKC/Ca2+/Calcineurin/Nuclear factor of activated T-cells; and EGF cellular receptors; and c) Gi alpha subunit-Giβγ) complexes which releases Gi that then simulates phospholipase C to cleave phosphatidylinositol triphosphate into inositol triphosphate that raises intracellular CaCa2 levels thereby regulating Calcium signaling pathways and diacylglycerol that activates certain protein kinase C enzymes )that phosphorylate and thereby regulate target proteins involved in cell signaling (see Protein kinase C#Function). Studies suggest that stimulation of Gsβγ complexes is required for activation of the Gqβγ- and Giβγ-dependent pathways. In certain cells, activation of IP also stimulates G12/G13-Gβγ G proteins to activate the Rho family of GTPases signaling proteins and Gi-Gβγ G proteins to activateRaf/MEK/mitogen-activated kinase pathways. Functions Studies using animals genetically engineered to lack IP and examining the actions of EP4 receptor agonists in animals as well as animal and human tissues indicate that this receptor serves various functions. It has been regarded as the most successful therapeutic target among the 9 prostanoid receptors. Platelets IP gene knockout mice (i.e. IP(-/-) mice) exhibit increased tendency to thrombosis in response to experimentally-induced Endothelium, a result which appears to reflect, at least in part, the loss of IP's anti-platelet activity. IP activation of animal and human platelets inhibits their aggregation response and as one consequence of this inhibition of platelet-dependent blood clotting. The PGI2-IP axis along with the production of nitric oxide, acting together additively and potentially synergistically, are powerful and physiological negative regulators of platelet function and thereby blood clotting in humans. Studies suggest that the PGI2-IP axis is impaired in patients with a tendency to develop pathological thrombosis such as occurs in obesity, diabetes, and coronary artery disease. Cardiovascular system IP activation stimulates the dilation of arteries and veins in various animal models as well as in humans. It increases the blood flow through, for example, the pulmonary, coronary, retinal and choroid circulation. Inhaled PGI2 causes a modest fall in diastolic and small fall in systolic blood pressure in humans. This action involves IP's ability to relax vascular smooth muscle and is