No abstract

In copper-deficient rats, oral intubation of copper increases the rate of ceruloplasmin synthesis without affecting general synthesis of plasma or liver proteins. It also restores the enzyme from half to full activity. Copper given by injection at doses commonly employed has additional nonspecific effects on protein synthesis and in some strains of rats produces severe hemolysis. In contrast to deficient rats, in normal rats copper does not elevate plasma ceruloplasmin unless hemolysis also occurs. Thus, at least in deficiency, copper availability controls the rate of synthesis, activation, and plasma concentration of cemloolasmin.

Rat intestinal mucosa gave low yields of ferritin purified by standard procedures. The resulting ferritin had less protein relative to iron and migrated faster electrophoretically than ferritin from other rat tissues. Pancreatic duct ligation reduced these differences, suggesting digestive enzyme attack during ferritin isolation. Even in ligated rats, ferritin accounted for only 5-10% of mucosal iron. However, shortly after giving 59FeCl3 orally, 50% of mucosal radioactivity occurred in cell sap, about equally distributed between ferritin and low-molecular-weight (chelated?) iron. No other cell sap components were 59Fe labeled. Iron may thus be transported as a chelate with which ferritin is in rapid equilibrium. Mucosal ferritin content increased with age and iron treatment and decreased with iron deficiency. The iron-deficient rats showed accelerated 59Fe uptake into blood with little mucosal retention. One day after administering parenteral iron to deficient rats, 59Fe transfer to blood became retarded but 59Fe now accumulated excessively in the mucosa, suggesting that iron status affects transport more rapidly at the serosal than at the mucosal cell surface. A scheme for control of iron absorption is presented.

This study was done to anatomically identify novel neurotransmitters localized to human intrinsic cardiac ganglia (ICG). Samples were collected from 8 patients during cardiothoracic surgery and processed for immunofluorescent detection of specific neuronal markers. Colocalization of markers was evaluated by confocal microscopy. All intrinsic cardiac neuronal somata showed immunoreactivity for the cholinergic marker choline acetyltransferase (ChAT). These somata were bordered by cholinergic varicosities, evident as punctate immunostaining for high affinity choline transporter. Moderate to intense staining for neuronal nitric oxide synthase (nNOS) was likewise associated with all ganglion neurons as well as some proximal axons and nerve fiber bundles connected to ICG. Many calcitonin gene‐related peptide (CGRP)‐immunoreactive nerve fibers were identified in ICG, often surrounding cholinergic/nitrergic neuronal somata. Fewer nerve fibers displayed substance P (SP)‐immunoreactivity, but all SP was colocalized with CGRP. These findings suggest that NO may play a prominent role in cholinergic transmission within the human heart, CGRP being another key neuromodulator in the human intrinsic cardiac nervous system. Identification of such novel mediators may lead to new paradigms for cardiac neuromodulation. Supported by the AHA SE Affiliate and the Canadian Institutes for Health Research.