Pathophysiological role influenced

Pathophysiology can influence muscarinic activity in other ways as well. Circulating autoantibodies against the second extracellular loop of cardiac M2 muscarinic receptors have been detected in some patients with idiopathic dilated cardiomyopathy and those afflicted with Chagas1 disease caused by the protozoan Trypanosoma cruzi. These antibodies exert parasympathomimetic actions on the heart that are prevented by atropine. In animals immunized with a peptide from the second extracellular loop of the M2 receptor, the antibody is an allosteric modulator of the receptor. Although their role in the pathology of heart failure is unknown, these antibodies should provide clues to the molecular basis of receptor activation because their site of action differs from the orthosteric site where acetylcholine binds (see Chapter 2). 

Biliary excretion plays smaller role in elimination of most drugs. However, pathophysiological conditions that cause cholestasis [11] or the genetics of transporters (e.g. OATP [12]) may influence PK of the compounds if biliary excretion is a significant component of their PK. 

While thromboxane A2 (TXA2) and prostaglandin H2 (PGH2) are produced by a large number of mammalian cell types and influence their function, the focus of this review will be primarily on their receptors in vascular smooth muscle and platelets. The potential role of these compounds in mediating physiological and pathophysiological processes in the cardiovascular system and platelets is covered in other chapters of this book. 

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