Brain distribution and evidence for both central and neurohormonal actions of cocaine- and amphetamine-regulated transcript peptide in Xenopus laevis.

We tested the hypothesis that, in the amphibian Xenopus laevis, cocaine- and amphetamine-regulated transcript peptide (CARTp) not only has widespread actions in the brain but also acts as a local factor in endocrine pituitary cells and/or is neurohemally secreted into the circulation to control peripheral targets. CARTp-immunoreactive cells occur in the olfactory bulb, nucleus accumbens, amygdala, septum, striatum, nucleus of Bellonci, ventrolateral nucleus, central thalamic nucleus, preoptic nuclei, and suprachiasmatic nucleus, and particularly in the medial pallium, ventromedial nucleus, hypothalamus, Edinger-Westphal nucleus, optic tectum, raphe nuclei, central gray, nucleus of the solitary tract, and spinal cord. From the hypothalamic magnocellular nucleus, CARTp-containing axons run to the neurohemal median eminence, and to the neural pituitary lobe to form neurohemal terminals, as shown by immunoelectron microscopy. Starvation increases the number of CARTp-cells in the optic tectum by 46% but has no effect on such cells in the torus semicircularis. CARTp does not affect in vitro release of alpha-melanophore-stimulating hormone from pituitary melanotrope cells. Our results support the hypothesis that in X. laevis, CARTp not only has multiple and not exclusively feeding-related actions in the brain but is also secreted as a neurohormone 1) into the portal system to control endocrine targets in the pituitary distal lobe and 2) from neurohemal axon terminals in the neural pituitary lobe to act peripherally. The differences in CARTp distribution between X. laevis and Rana esculenta may be related to different environmental and physiological conditions such as feeding, sensory information processing, and locomotion.