Distribution of cocaine- and amphetamine-regulated transcript peptide in the guinea pig intrinsic cardiac nervous system and colocalization with neuropeptides or transmitter synthetic enzymes

J Comp Neurol. 2001 Oct 8;439(1):73-86. doi: 10.1002/cne.1336.


This study was conducted to establish the presence of cocaine- and amphetamine-regulated transcript peptide (CARTp) immunoreactivity in neurons and fibers within guinea pig atrial whole-mount preparations containing the intrinsic cardiac ganglia. Many cardiac ganglia, but not all, in a given whole-mount preparation, were innervated by CARTp-immunoreactive (IR) fibers. Following explant culture of whole mounts for 72 hours, the CARTp-IR fiber networks were absent, but the number of CARTp-IR neurons was increased markedly. These observations suggested that the majority of the CARTp-IR fibers in the intracardiac ganglia were derived from sources extrinsic to the heart. In control whole-mount preparations, very few CARTp-positive neurons were present. The few intrinsic CARTp-IR neurons also exhibited choline acetyltransferase (ChAT) immunoreactivity, indicating that they make up a small subpopulation of cholinergic postganglionic neurons. Some CARTp-IR neurons also exhibited nitric oxide synthase (NOS) immunoreactivity, indicating that they were nitrergic as well. We compared the immunohistochemical staining patterns of CARTp-IR fibers with the staining patterns of a number of other neurotransmitters or neurotransmitter synthetic enzymes that mark specific extrinsic inputs. The CARTp-IR fibers were not immunoreactive for ChAT, tyrosine hydroxylase, calcitonin gene-related peptide, or substance P. However, virtually all CARTp-IR fibers exhibited immunoreactivity to neuronal NOS (a marker for nitric oxide-producing neurons). CARTp-IR cells and NOS-IR cells were present in the nodose ganglia. In addition, CARTp-IR neurons in the nodose also were stained positively for NADPH-diaphorase. Thus, we propose that most CARTp-IR fibers within the guinea pig intrinsic cardiac ganglia are vagal afferent fibers that also contain NOS.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Afferent Pathways / physiology
  • Animals
  • Choline O-Acetyltransferase / metabolism
  • Enzymes / metabolism*
  • Female
  • Ganglia / metabolism
  • Ganglia, Spinal / metabolism
  • Guinea Pigs
  • Heart Conduction System / metabolism*
  • Male
  • Nerve Fibers / metabolism
  • Nerve Tissue Proteins / metabolism*
  • Neuropeptides / metabolism*
  • Neurotransmitter Agents / biosynthesis*
  • Synaptic Transmission / physiology
  • Tissue Distribution
  • Vagus Nerve / physiology


  • Enzymes
  • Nerve Tissue Proteins
  • Neuropeptides
  • Neurotransmitter Agents
  • cocaine- and amphetamine-regulated transcript protein
  • Choline O-Acetyltransferase