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Serotonin and carcinoid tumors.

The enterochromaffin (EC) cell system is distributed throughout the entire gastrointestinal tract. Enterochromaffin cells are the major source of intestinal serotonin (5-HT), but separate subpopulations of EC cells may synthesize and store peptides as substance P (SP), motilin, and enkephalin as well. Of special interest is that 5-HT and SP, which may coexist in EC cells, have several functional similarities, i.e., inhibition of gastric acid secretion, stimulation of intestinal motility, and secretion of water and electrolytes. Carcinoid tumors are derived from the gut endocrine system. Depending on site of origin, carcinoids are divided into foregut, midgut, and hindgut derivatives with different clinical symptoms. A common biochemical feature of midgut carcinoids is the production of 5-HT and SP. Histochemically, midgut carcinoids are characterized by the argentaffin reaction--a direct reduction of silver salts owing to 5-HT. Specific antisera for the immunocytochemical demonstration of secretory products are available as well. Despite their relative infrequency, carcinoids are the most common small intestinal tumors. The common appendix tumors generally have a benign clinical course, whereas the small intestinal tumors have different growth patterns and frequently metastasize with increasing size, and may thus give rise to the carcinoid syndrome (diarrhea, facial flush, right-sided cardiac valvular disease, and asthma). Carcinoid symptoms first appear when hepatic inactivation of 5-HT is exceeded, unless the carcinoid has an extraintestinal localization, for example, ovarian lesions may elicit symptoms in the absence of hepatic disease owing to direct secretion into systemic circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

APUD Cells↗

[Morphological evidence of celiac ganglion hyperfunction in spontaneous hypertension in rats].

To elucidate the role of the autonomous nervous system in formation of a specific renal "resetting", typical for arterial hypertension, in 8-week-old spontaneously hypertensive rats, a study was made of the morphology of the celiac ganglion as one of the main sources of renal innervation. Light and fluorescent microscopy demonstrate the hypertrophy of the neurons and their nuclei, an increase in the whole ganglion volume and the volume density of the SIF cells. This evidence for hyperactivity of the celiac ganglion attests to the involvement of the renal nervous system in the structural and functional reorganization ("resetting") at the early stages of hypertension as well as a manifestation of hyperactivity of the nervous system in this disease.

Animals↗

Intra and juxtavagal paraganglia: a topographical, histochemical, and ultrastructural study in the human.

The topographical, ultrastructural, and histochemical features of 23 human vagal paraganglia were analyzed. Nineteen of the 23 paraganglia were found in previously unreported sites; 18 of the 19 were in the cervical part of the nerve, between the carotid bifurcation and the superior thoraco-cervical inlet, and one paraganglion was located in the retrothyroidal part of the left inferior laryngeal nerve. The results of ultrastructural studies (2 cases), the histochemical and formaldehyde-induced-fluorescence studies (3 cases), and specific acetylcholinesterase activity (one case) demonstrate that these structures fulfill many of the modern criteria for paraganglionic tissue. In addition to paraganglia, single, isolated neurons or true micro-ganglia were always found along the trunk and branches of the vagus nerve when multiple sections were examined.

Adolescent↗

Perinatal development of galanin-like immunoreactivity in chromaffin tissues of the rabbit.

We have analyzed the perinatal development of galanin-like immunoreactivity (GAL-LI) and catecholamines (CA) in the paraaortal paraganglia (PGGL) and adrenal glands. In the PGGL, the tissue content of GAL-LI was highest on the day of birth and decreased postnatally. The fetal levels were lower than at birth. In contrast, the content of CA in the PGGL increased with age. In the adrenal glands, the contents of both GAL-LI and CA also increased with age. During the first postnatal week the contents of both GAL-LI and CA in the PGGL were markedly higher than in the adrenal glands. Chromatographic analysis of GAL-LI in extracts of fetal and postnatal rabbit PGGL, respectively, indicated that most of the GAL-LI from both age groups co-eluted with synthetic porcine GAL. An additional, apparently more polar, component was also detected at both ages, which may represent a differently processed form of the peptide. The high content of GAL-LI in the PGGL at birth may reflect an enhanced synthesis associated with birth.

Adrenal Glands↗

Paraganglia of the bladder.

Normal paraganglia containing high amounts of catecholamines are a constant feature of the wall of the bladder in elderly men. The paraganglia in this location might give rise to pheochromocytomas. The importance of the local endocrine effects in the regulation of the muscular tone in the bladder is discussed.

Chromaffin System↗

Hypothesis: the bronchial Kulchitsky (K) cell as a source of humoral biologic activity.

The bronchial Kulchitsky cells are scattered specific cells which lie close to the basement membrane of the bronchi and bronchioles. Electron microscopy reveals that they contain electron-dense granules similar to that seen in cells with a known endocrine function. In addition, experimentally induced degranulation of the K cell suggestive of a secretory process, and the likelihood that these cells are precursors of small cell lung carcinoma (which often elaborates humoral substances) has led to the postulate that this bronchial cell serves a humoral role of either a paracrine or endocrine nature. We have found that the bronchial K cell of man contains a calcitonin-like polypeptide which, immunologically and chemically, is not dissimilar to the hormone produced by the C cells of human thyroid. This finding may help explain the persistence of serum immunoreactive calcitonin (iCT) after total thyroidectomy, the fact that thyroidectomized man does not manifest any profound alteration of calcium metabolism, and why small cell cancer of the lung is frequently associated with hypercalcitonemia. In addition, the finding of K cell hyperplasia in chronic bronchitis and emphysema may explain the occurrence of hypercalcitonemia in patients with these diseases and some lung cancers of cell types other than the small cell variety. Further studies are needed to elucidate the role of K cell iCT, and to determine what other hormones might also be elaborated by this diffuse system of bronchial cells.

Bronchi↗

Ganglion cells and paraganglionic cells in the developing superior cervical ganglion of normal and p-chlorophenylalanine treated rats.

Ganglion cells and paraganglionic (PG) cells in the developing rat superior cervical ganglion were studied following postnatal treatment with p-chlorophenylalanine (pCPA) for 5 to 8 days. Litter mates, injected with saline solution, served as controls. Ganglion cells of control animals were differentiated ultrastructurally according to L. Eränkö (1972a) into late sympathicoblasts and young sympathetic nerve cells. In both maturation stages treatment with pCPA caused marked swelling of mitochondria, concomitant with minor changes of other cell organelles. Parallel to the ultrastructural alterations, fluorescence microscopy and cytophotometry revealed a slight diminution of diffuse fluorescence intensity in sympathetic neurons as the expression of a mainly extragranular amine depletion. In distinction from ganglion blocking agents the alterations are regarded as a general toxic effect of pCPA upon maturing sympathetic neurons, which secondarily influences catecholamine storage sites. Following treatment with pCPA, in PG-cells an alteration of mitochondria was scarcely to recognize. Specific granules were distinctly decreased in number, in some cases to an almost complete degree. Concordant to ultrastructural observations a marked diminution of fluorescence intensity was demonstrable in SIF-cells. In addition in these elements the fluorescence spectrum shifted towards the green field. Fluorescence cytophotometric evaluations confirmed the optical impression. Provided, that PG-cells, demonstrated with electron microscopy, are identical with SIF-cells in fluorescence microscopy, the results are discussed on the basis of a specific decrease of primary catecholamines due to an enzyme inhibition involved in catecholamine synthesis.

Animals↗