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

J Comp Neurol. 2005 Nov 21;492(3):370-9. doi: 10.1002/cne.20745.


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 nonnoradrenergic. Adult human sweat gland innervation, however, is not only cholinergic but coexpresses all of the proteins required for full noradrenergic function as well, including tyrosine hydroxylase, aromatic amino acid decarboxylase, dopamine beta-hydroxylase, and the vesicular monoamine transporter VMAT2. Thus, cholinergic/noradrenergic cotransmission 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 cophenotype. Cholinergic/noradrenergic coexpression is absent from other portions of the human sympathetic nervous system but is extended in the parasympathetic nervous system to intrinsic neurons innervating the heart. These observations suggest a mode of autonomic regulation, based on corelease of norepinephrine and acetylcholine at parasympathocardiac, sudomotor, and selected vasomotor neuroeffector junctions, that is unique to the primate peripheral nervous system.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / metabolism*
  • Animals
  • Autonomic Nervous System* / anatomy & histology
  • Autonomic Nervous System* / chemistry
  • Autonomic Nervous System* / metabolism
  • Female
  • Heart / innervation
  • Humans
  • Immunohistochemistry
  • Macaca mulatta
  • Male
  • Mice
  • Neurons / chemistry
  • Neurons / cytology
  • Neurons / metabolism
  • Norepinephrine / metabolism*
  • Phenotype
  • Rats
  • Rats, Wistar
  • Sweat Glands / innervation*
  • Vesicular Acetylcholine Transport Proteins / metabolism
  • Vesicular Monoamine Transport Proteins / metabolism


  • Slc18a2 protein, mouse
  • Slc18a3 protein, mouse
  • Vesicular Acetylcholine Transport Proteins
  • Vesicular Monoamine Transport Proteins
  • Acetylcholine
  • Norepinephrine