Dopamine outside the brain: The eye, cardiovascular system and endocrine pancreas

Dopamine (DA) and DA receptors (DR) have been extensively studied in the central nervous system (CNS), but their role in the periphery is still poorly understood. Here we summarize data on DA and DRs in the eye, cardiovascular system and endocrine pancreas, three districts where DA and DA-related drugs have been studied and the expression of DR documented. In the eye, DA modulates ciliary blood flow and aqueous production, which impacts on intraocular pressure and glaucoma. In the cardiovascular system, DA increases blood pressure and heart activity, mostly through a stimulation of adrenoceptors, and induces vasodilatation in the renal circulation, possibly through D1R stimulation. In pancreatic islets, beta cells store DA and co-release it with insulin. D1R is mainly expressed in beta cells, where it stimulates insulin release, while D2R is expressed in both beta and delta cells (in the latter at higher level), where it inhibits, respectively, insulin and somatostatin release. The formation of D2R-somatostatin receptor 5 heteromers (documented in the CNS), might add complexity to the system. DA may exert both direct autocrine effects on beta cells, and indirect paracrine effects through delta cells and somatostatin. Bromocriptine, an FDA approved drug for diabetes, endowed with both D1R (antagonistic) and D2R (agonistic) actions, may exert complex effects, resulting from the integration of direct effects on beta cells and paracrine effects from delta cells. A full comprehension of peripheral DA signaling deserves further studies that may generate innovative therapeutic drugs to manage conditions such as glaucoma, cardiovascular diseases and diabetes.