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Biomedical subjects

H M Greven

Publications and source records attributed to H M Greven.

At least 19 recordsLinked to original sources
PubMed1985

Inhibition of gamma-endorphin generating endopeptidase activity of rat brain by peptides: structure activity relationship.

gamma-Endorphin generating endopeptidase (gamma EGE) activity is an enzyme activity which converts beta-endorphin into gamma-endorphin and beta-endorphin-(18-31). The inhibitory potency on gamma EGE activity of neuropeptides and analogues or fragments of neuropeptides was tested. Dynorphin-(1-13) (IC50: 0.14 microM), human beta-endorphin-(1-31) (IC50: 15.5 microM), porcine ACTH-(1-39) (IC50: 6.3 microM), and substance P (IC50: 26 microM) had an inhibitory activity on gamma EGE activity. beta-Endorphin-(18-31) (IC50: 0.35 microM) but not gamma-endorphin potently inhibited gamma EGE activity. The IC50 of poly (Lys)40-60 was 0.8 microM. It is concluded that 1) gamma EGE activity is strongly inhibited by its product beta-endorphin-(18-31), 2) the enzyme is strongly inhibited by peptides with an aromatic amino acid at the NH2-terminal and/or basic amino acids in the COOH-terminal of the peptide chain.

Amino Acid Sequence↗
PubMed1983

Oxytocin is a precursor of potent behaviourally active neuropeptides.

An oxytocin fragment which accumulated during the incubation of oxytocin with brain synaptic membranes was chemically characterized as the hexapeptide pGlu-Asn-Cys(Cys)-Pro-Leu-Gly-NH2 [( pGlu4, Cyt6]OXT-(4-9]. This peptide was approximately a hundred times more potent than oxytocin in attenuating memory consolidation as tested in a passive avoidance test situation; the dose-response relationship was bell-shaped. The des-glycinamide derivative [pGlu4, Cyt6]OXT-(4-8) was nearly as active, but showed a linear dose-response relationship. The data indicate that oxytoxin can act as precursor for potent behaviourally active neuropeptides.

Animals↗
PubMed1983

A major metabolite of arginine vasopressin in the brain is a highly potent neuropeptide.

A peptide that accumulated as the major product during the proteolysis of arginine vasopressin by rat brain synaptic membranes was isolated and its structure was shown to be the hexapeptide pGlu-Asn-Cys(Cys)-Pro-Arg-Gly-NH2. When administered intracerebroventricularly in extremely low doses, this vasopressin fragment and its desglycinamide derivative facilitated memory consolidation in a passive avoidance situation. These vasopressin metabolites, which are devoid of pressor activity, constitute highly potent neuropeptides with selective effects on memory and related processes; they are activated via proteolytic processing of vasopressin by brain peptidases.

Amino Acid Sequence↗
PubMed1981

Gamma-melanotropin and brain function.

In view of the close structural similarity between the pro-opiocortin fragment, gamma-MSH, and ACTH/MSH-type peptides, the behavioural profile of gamma-MSH was explored. Attention was first focused on behavioural procedures in which ACTH/MSH-related neuropeptides have been found effective. It was found that gamma-MSH and ACTH-like neuropeptides had opposite effects on avoidance behaviour. In this respect the activity of gamma-MSH resembles that of opiate antagonists rather than that of beta-endorphin. Accordingly, ACTH(1-24) induced excessive grooming which is blocked by opiate antagonists and is attenuated by gamma-MSH. In addition, gamma-MSH injected into the periaqueductal grey matter of the brainstem of opiate-naive rats elicited symptoms reminiscent of those seen after opiate withdrawal. Gamma-MSH attenuated several effects of intracerebroventricularly administered beta-endorphin (e.g. antinociception, hypothermia, alpha-MSH release) and decreased the acquisition of heroin self-administration. Although gamma-MSH at rather high doses displaced naloxone from its specific binding sites in brain homogenates, it did not interfere with beta-endorphin-induced effects on in vitro muscle preparations (guinea-pig ileum; rat rectum). Interestingly, gamma-MSH induced relaxation of the rat rectum in vitro. It is postulated that gamma-MSH may attenuate beta-endorphin-induced effects by acting via gamma-MSH receptor sites (functional antagonism), although a pharmacological antagonism cannot be excluded as yet.

Adrenocorticotropic Hormone↗
PubMed1975

Correlation between structure, behavioral activity and rate of biotransformation of some ACTH4-9 analogs.

The effect of substitutions in adrenocorticotropin (ACTH4-9) on extinction of pole-jumping avoidance behavior in intact rats was investigated systemically at two-dose levels. Simultaneous introduction of 4-methionine sulfoxide and 5-D-lysine, in combination with 9-phenylalanine, led to a 1000-fold increase in behavioral potency. The same substitutions induced a 1000-fold decrease in melanocyte-stimulating hormone activity. Incubations of 14-C-labeled ACTH4-9 analogs, prepared by reductive methylation, were carried out with plasma and brain extracts. The resulting metabolites were separated by paper electrophoresis and paper chromatography. The concentrations of nonmetabolized hexapeptides, which appeared to be almost entirely responsible for behavioral activity, were determined as a function of incubation time. The in vitro half-life of intact hexapeptides correlated with their behavioral activity. Therefore, the increase in behavioral potency as a result of amino acid substitutions can be explained, at least partly, by increased resistance against biotransformation.

Adrenocorticotropic Hormone↗