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Biomedical subjects

A Munck

Publications and source records attributed to A Munck.

153 records · Page 9Linked to original sources
PubMedDate not supplied

Glucagon-37 (oxyntomodulin) and glucagon-29 (pancreatic glucagon) in human bowel: analysis by HPLC and radioreceptorassay.

A method for assaying specifically the biologically active peptides Glucagon-37 (G-37/Oxyntomodulin/bioactive Enteroglucagon) and Glucagon-29 (G-29/pancreatic Glucagon) has been developed by use of high performance liquid chromatography (HPLC) of crude tissue extracts followed by radioreceptorassay in liver membranes. The peaks observed with this method in samples from human bowel have also been analysed in two other assays: stimulation of cyclic AMP accumulation in gastric glands and radioimmunoassay. Owing to the different patterns of activity of porcine G-37 and G-29 in these assays, the comparison of the data obtained allows to discriminate between the two peptides. The same behaviour in both HPLC and the three assays of the human peaks on one hand and the porcine peptides on the other strongly suggests that human intestine contains a very similar or the same molecules as that isolated from the porcine tissues. Whatever the portion of small intestine, G-37 represented ca 90% of G-37 + G-29. A decreasing concentration gradient of both G-37 and G-29 was also observed from ileum to descending colon.

Animals↗
PubMedDate not supplied

Adrenergic versus VIPergic control of cyclic AMP in human colonic crypts.

The actions of catecholamines on VIP-induced cyclic AMP is studied in human colon. We show that: (1) Epinephrine in the 10(-7)-10(-3) M concentration range (ED50 = 11.10(-6) M) inhibits VIP-induced cyclic AMP rise in isolated colonic epithelial cells; the maximal inhibition reaches 30% of VIP effect; epinephrine alters the efficacy of the peptide and does not modify its potency; epinephrine also reduces the basal cyclic AMP level. (2) The inhibition is found with other alpha adrenergic agonists with the order of potencies epinephrine greater than norepinephrine greater than phenylephrine. Clonidine has a poor intrinsic activity but antagonizes the action of epinephrine. (3) The inhibition of VIP action by epinephrine is reversed by the alpha antagonists dihydroergotamine, phentolamine and the alpha 2 antagonist yohimbine, while unaffected by the beta antagonist propranolol and the alpha 1 antagonist prazosin, (4) Epinephrine inhibits VIP-stimulated adenylate cyclase activity in preparations of colonic plasma membranes. Thus catecholamines exert through an alpha 2 adrenoreceptor a negative control on basal and VIP-stimulated cyclic AMP formation in human colon. We suggest that colonic cyclic AMP metabolism undergoes a dual control: VIPergic, activator and adrenergic, inhibitor.

Adenylyl Cyclases↗
PubMedDate not supplied

Glucocorticoid receptors lacking hormone-binding activity are bound in nuclei of ATP-depleted cells.

The glucocorticoid receptor binding capacity of rat thymus cells disappears when the cells are depleted of ATP by anaerobiosis, and rapidly reappears when ATP levels are restored. Loss and recovery of binding capacity occurs even when protein synthesis is suppressed with cycloheximide. In view of this and similar work in other cell systems, we proposed that in cells deprived of ATP the receptor is present in a form--the 'null receptor' form, as we shall call it--that cannot bind hormone. Although many subsequent observations support this idea, no direct evidence has appeared for the existence of the null receptor. We have attempted to detect the null receptor in WEHI-7 mouse thymoma cells with a monoclonal antibody to the glucocorticoid receptor. Here we report that the null receptor is bound in the nuclei of ATP-depleted cells, and is present in amounts comparable to those of receptors in normal cells.

Adenosine Triphosphate↗
PubMedDate not supplied

Effects and receptors of glucocorticoids in rat thymus cells and human peripheral lymphocytes.

Glucocorticoids are widely used for therapeutic purposes and have many toxic side effects. It seems likely that their physiological, therapeutic, and toxic effects are exerted through similar receptors and may be inherently inseparable. Lymphoid cells are targets for all these effects. With rat thymus cells in vitro, glucocorticoids immediately bind to cytoplasmic receptors, which are translocated to the nucleus, where they apparently induce messenger RNA for specific proteins that rapidly inhibit glucose transport. Protein and RNA metabolism are inhibited more slowly and eventually the cells die. The rate of formation of nuclear complexes and the timing of the hypothetical RNA-synthetic step are such as to suggest that the hormone-receptor complexes stimulate RNA synthesis in proportion to the rate at which they bind to nuclear sites rather than in proportion to the number of nuclear sites occupied. With normal peripheral human lymphocytes the rates of formation of hormone-receptor complexes are similar to those in rat thymocytes. The rate of onset of inhibition of glucose transport is lower, however, as is the rate of cytolysis. In human peripheral lymphocytes stimulated to undergo blast transformation with concanavalin A there is a dramatic increase in the number of glucocorticoid receptor sites per cell. This increase may be associated with a stage of the normal cell cycle, the mitogen stimulus inducing partial synchronization of the cell population. It has not been found, contrary to widespread belief, that mitogen stimulation renders cells insensitive to glucocorticoids.

Animals↗