Distribution and possible origin of neuropeptide-containing nerve elements in the mammalian liver

The intrahepatic distribution of nerve fibres is highly species dependent, therefore we searched for a species where the innervation pattern is similar to that of the human liver. Livers of rats, cats, guinea pigs and humans were used. The different nerve elements were identified by ABC immunohistochemistry and analysed semiquantitatively. Large numbers of neuropeptide Y (NPY) and dopamine-β-hydroxylase immunoreactive (IR) nerve fibres were observed in the human and guinea pig liver, and they were in close contact with portal triads, central veins and ran parallel with liver sinuses. A few substance P, somatostatin and vasoactive intestinal polypeptide IR nerve fibres were also detected intralobularly, while galanin nerve fibres were only observed around portal triads. In the rat liver only a few NPY-positive nerve fibres were found, exclusively in portal tracts. Some nerve cell bodies (IR for NPY and somatostatin) were also found in the liver of guinea pigs, young cats and humans, therefore some of the nerve terminals might originate from these intrinsic ganglia. It can be concluded that the innervation pattern of the guinea pig liver shows the highest similarity to that of the human liver.

Distribution of peptidyl-glycine alpha-amidating mono-oxygenase (PAM) enzymes in normal human lung and in lung epithelial tumors.

C-terminal alpha-amidation is a post-translational modification necessary for the biological activity of many regulatory peptides produced in the respiratory tract. This modification is a two-step process catalyzed by two separate enzyme activities, both derived from the peptidyl-glycine alpha-amidating mono-oxygenase (PAM) precursor. The distribution of these two enzymes, peptidyl-glycine alpha-hydroxylating monoxygenase (PHM) and peptidyl-alpha-hydroxyglycine a amidating lyase (PAL), was studied in the normal lung and in lung tumors using immunocytochemical methods and in situ hybridization. In normal lung the enzymes were located in some cells of the airway epithelium and glands, the endothelium of blood vessels, some chondrocytes of the bronchial cartilage, the alveolar macrophages, smooth muscle cells, neurons of the intrinsic ganglia, and in myelinated nerves. A total of 24 lung tumors of seven different histological types were studied. All cases contained PAM-immunoreactive cells with various patterns of distribution. All immunoreactive cells were positive for the PHM antiserum but only some of them for the PAL antiserum. The distribution of PAM co-localizes with some other previously described amidated peptides, suggesting that amidation is an important physiological process taking place in the normal and malignant human lung tissue.

Two sympathetic nerve supplies to brown adipose tissue of the rat

The fluorescent histochemical technique of Falck for demonstrating catecholamines in sympathetic nerve fibers was modified for use in brown fat. In normal interscapular and mediastinal brown fat, the nerve fibers surrounded the arterial Mood vessels and all parenchymal cells. Both immunosympathectomy and surgical denervation gave an almost identical histological picture of massive loss of nerves from the blood vessels only. The parenchymal innervation remained intact. The blood vessels retained single isolated nerve fibers, which were relatively more numerous on the small vessels and which were connected with the parenchymal innervation. After sympathetic nerve fibers were depleted of catecholamines by treating the rat with reserpine, the parenchymal nerves reestablished catecholamine fluorescence at a faster rate than the blood vessel nerves. Intrinsic (tissue) ganglia in the brown fat were resistant to immunosympathectomy. These ganglia contained cells which were very brightly fluorescent. These results indicate that there are two anatomically, immunologically, and pharmacologically different nerve supplies to brown fat, one to the blood vessels and the other predominantly to the parenchyma. It was concluded that the parenchymal nerve supply is derived from the intrinsic ganglia via 'short' adrenergic neurons, and the blood vessel innervation is derived from the sympathetic chain via 'long' adrenergic neurons.

Characterization of the metabolic gradient in cat small intestine by layer fractionation

Gradations in oxygen consumption were observed in preparations of intact segments and in layer fractions of cat small intestine, which were excised following Nembutal anesthesia. Mechanical separation of the intestinal segments into layers provided a means for localization of these gradients within specific components of the intestinal wall. Gradients were found in segments of the submucosal and mucosal layers and in segments composed of circular muscle, submucosa, and mucosa; but none was observed in segments of the isolated circular muscle layer. Inactivation of one or both intrinsic ganglionic plexuses by mechanical separation abolished the gradient associated with the circular muscle layer. The tentative explanation of these findings is that the existence of a metabolic gradient within the intestine arises from two sources: a) a graded activity within the submucosal mucosal layers and b) a sharply graded differential oxygen consumption within the muscular layers which is controlled by the functional activity of the intrinsic ganglia.