Coexpression of cholinergic and noradrenergic phenotypes in human and nonhuman autonomic nervous system

It has long been known that the sympathetic innervation of the sweat glands is cholinergic in most mammalian species, and that during development, rodent sympathetic cholinergic sweat gland innervation transiently expresses noradrenergic traits. We show here that some noradrenergic traits persist in cholinergic sympathetic innervation of the sweat glands in rodents, but that lack of expression of the vesicular monoamine transporter renders these cells functionally non-noradrenergic. Adult human sweat gland innervation, however, is not only cholinergic, but co-expresses all of the proteins required for full noradrenergic function as well, including tyrosine hydroxylase, aromatic amino acid decarboxylase, dopamine ß-hydroxylase, and the vesicular monoamine transporter VMAT2. Thus, cholinergic/noradrenergic co-transmission is apparently a unique feature of the primate autonomic sympathetic nervous system. Furthermore, sympathetic neurons innervating specifically the cutaneous arteriovenous anastomoses (Hoyer Grosser organs) in humans also possess a full cholinergic/noradrenergic co-phenotype. Cholinergic/noradrenergic co-expression is absent from other portions of the human sympathetic nervous system, but is extended in the parasympathetic nervous system to the intrinsic neurons innervating the heart. These observations suggest a mode of autonomic regulation, based on co-release of norepinephrine and acetylcholine at parasympathocardiac, sudomotor, and selected vasomotor neuroeffector junctions, that is unique to the primate peripheral nervous system.