Extraneural Tissues

Deposition of metachromatio material in tissues other than the central nervous system was noted quite early by Witte (1921) in the anterior lobe of the pituitary and in liver, renal tubuli and testes by Norman (1947) in the gallbladder wall and renal tubuli, and by Einarson and Neel (1942) in the kidneys. In a case described by Kaltenbach (1922), hepatosplenomegaly was found at autopsy, but metachromasia was not looked for. 

While glomeruli are normal, the tubular cells, particularly of the loop of Henle, of the distal convoluted tubuli, and of the collecting system may be loaded with 

The morphologic substrate for gallbladder dysfunction is cytoplasmic meta-chromasia of the mucosal cells. The villi are distended by accumulation of pha-gocytizing histiocytes, which are also filled with metachromatic lipid. This material may also be seen in small medullated nerves of deeper layers of the gallbladder wall. In addition, phagocytes contain cholesterol and other lipid which stains with Scarlet-red. 

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A second, nonchemical, NE-terminating process is simply diffusion away from the synaptic area. The quantitative significance of this is difficult to gauge since diffusion also brings the NE molecules into the clutches of the extraneural metabolism enzymes catechol-O-methyltransferase (COMT) and MAO. Here the catecholamines are taken up, Uptake 2(U2), into extraneural tissue and degraded. Unlike the neuronal reuptake process (Ui), this does not represent amine preservation. 

In summary, unlike with cholinergic neurons, where termination of action is rapidly accomplished by a single efficient process, hydrolysis of the neurotransmitter by AChE, in the case of catecholamines, a multiple of processes occur simultaneously. A major intraneural reuptake process, a dilution effect by diffusion away from the synaptic cleft, which includes uptake (U2) into extraneural tissue, oxidative deamination by MAO and m-methylation of the catechol moiety by COMT. 

The drug is not significantly affected by MAO, but it is 3-methylated by COMT in the lung and other extraneural tissue. Frequently, repeated administration can lead to fastness or a loss of bronchodilating effect, which may in part be due to the accumulating 3-methoxy metabolite, a weak (3-blocker theoretically capable of causing broncho-constriction. In any case, IPR has become the prototype compound against which all the newer bronchodilators are compared. 

Engler, D., Scanlon, M.F. and Jackson, I.M.D. (1981) Thyrotropin releasing hormone in the systemic circulation of the neonatal rat is derived from the pancreas and other extraneural tissues. J Clin Invest 67 800. 

The presence of a ganglioside containing L-fucose in ox brain is further evidence of the relation between gangliosides in neural and extraneural tissues. 

Hematoside is the major sialic acid-containing sphingoglycolipid of extraneural tissue. 

Finne, J., Bitter-Suermann, D., Goridis, C., and Finne, U., 1987, An IgG monoclonal antibody to group B meningococci cross-reacts with developmentally regulated polysialic acid units of glycoproteins in neural and extraneural tissues, J. Immunol. 138 4402-4407. 

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