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V M Wiegant

Publications and source records attributed to V M Wiegant.

At least 145 records · Page 8Linked to original sources
PubMed1980

Selective conversion of beta-endorphin into peptides related to gamma- and alpha-endorphin.

beta-Endorphin (beta-LPH61-91) is a well known endogenous opioid ligand. It and related peptides have recently been implicated in the control of adaptive behaviour. Smaller beta-endorphin fragments appeared to be more active moieties than the parent molecule in a number of behavioural situations. Their effects seemed to occur independently of interaction with opiate receptor sites in the brain. Moreover, elimination of the opiate-like properties of gamma-endorphin (beta-LPH61-77) by removing the N-terminal amino acid yielded des-tyrosine-gamma-endorphin (beta-LPH62-77, dT gamma E) which had greater behavioural activity than gamma-endorphin. The CNS effects of dT gamma E resembled those of neuroleptic drugs in several test systems. alpha-Endorphin (beta-LPH61-76) exerted effects opposite to those of dT gamma E and in some aspects its activity was comparable to that of psychostimulant drugs. This opposition of effects suggests that a balance between gamma- and alpha-type endorphins is involved in the control of brain function. We report here that either gamma-endorphin and dT gamma E or alpha-endorphin and des-tyrosine-alpha-endorphin (beta-LPH62-76, DT alpha E) can be formed preferentially from beta-endorphin by enzymes associated with an enriched synaptosomal plasma membrane fraction from brain. It is suggested that these enzymes have a role in brain homeostatic mechanisms by regulating the generation of these substances.

Animals↗
PubMed1979

ACTH-like neurotropic peptides: possible regulators of rat brain cyclic AMP.

The influence of behaviorally active, N-terminal fragments of ACTH on the accumulation of cAMP in rat brain investigated in broken cell preparations of subcortical tissue, in slices of neostriatum and in vivo. ACTH1--24 has a biphasic effect on the activity of adenylate cyclase in broken cell preparations of rat brain subcortical tissue: concentrations below 25 micrometer stimulated, whereas concentrations of 0.1 mM and higher inhibited adenylate cyclase activity. The magnitude of the stimulation was dependent on the concentrations of ATP and Mg2+ in the incubation medium. Structure activity studies revealed that at a concentration of 10(-4) M ACTH1--16-NH2 and ACTH4--7 also inhibited the activity of adenylate cyclase, whereas ACTH11--24, ACTH1--10, ACTH4--10, [D-Phe7]ACTH1--10 and [D-Phe7]ACTH4--10 were inactive in this respect. Addition of 0.8 mM EGTA but not of 0.25 mM Ca2+ prevented the inhibition by 10(-4) M ACTH1--24. GMP-N-P (10(-5) M), naltrexone (10(-3) M) and ergometrine (10(-3) M) did not influence the inhibitory effect. ACTH1--24 enhanced the accumulation of cAMP in slices from rat brain neostriatum in a dose-dependent manner. This effect was already maximal 7.5 min after the addition of the peptide and was potentiated by isobutylmethylxanthine, a potent inhibitor or phosphodiesterase. Intraventricular injection of 1 microgram ACTH1--16-NH2 in rats significantly elevated (+ 27%) the concentration of cAMP in the septal region 60 min after the injection of the peptide. The results are discussed in terms of a possible involvement of cAMP as a second messenger in the central nervous system for N-terminal fragments of ACTH.

Adenosine Triphosphate↗
PubMed1978

Distinct dopaminergic systems in ACTH-induced grooming.

Excessive grooming behavior induced in rats by intraventricular injection of ACTH1-24 was inhibited by selective pharmacological manipulation of two functionally distinct types of dopaminergic terminals (DAe and DAi) in the neostriatum or the nucleus accumbens. It is concluded that when ACTH1-24 produces the behavioral response it modulates the activity of both the DAe and the DAi systems.

Adrenocorticotropic Hormone↗
PubMed1978

Endogenous phosphorylation of rat brain synaptosomal plasma membranes in vitro: some methodological aspects.

The time course of endogenous phosphorylation in vitro of total or separated synaptic plasma membrane proteins (SPM) has been correlated with that of hydrolysis of the phosphate donor (ATP) in the incubation medium. The ATP/SPM ratio in the medium was varied. In a low-ratio medium (7.5 muM ATP; 2.2 microgram SPM/microliter) a complete hydrolysis of ATP occurred almost instantaneously as was measured by the release of free phosphate in and the disappearance of ATP from the medium. As a consequence, only a very short peak of phosphorylation, followed by dephosphorylation was observed. However, when higher ATP/SPM ratios were used (200 muM ATP; 0.4 microgram SPM/microliter and 500 muM ATP; 0.4 microgram SPM/microliter), the incorporation of phosphate into SPM proteins was linear for 20 sec, and the maximum level of phosphate incorporation was increased. Similar results were obtained after separation of 32P-labeled phosphoproteins by slab gel electrophoresis. However, analysis of the autoradiographs obtained from one SPM preparation under different ATP/SPM ratios revealed dependence of phosphorylation of individual protein bands on the conditions used.

Adenosine Triphosphate↗
PubMed1978

ACTH-induced inhibition of endogenous rat brain protein phosphorylation in vitro: structure activity.

ACTH1--24 inhibits the endogenous phosphorylation in vitro of distinct SPM protein bands. Using N-terminal fragments of ACTH, the structure-activity requirements for this effect were studied. A rather complex interaction of the ACTH fragments with endogenous SPM phosphorylation was observed. The effects were not only dependent on the primary structure of the peptide used, but also on the protein band studied and the ATP/SPM ratio used in the incubation system. ACTH1--24 did not interfere with the ATP-hydrolyzing activity of the SPM preparation, nor did it influence the endogenous phosphatase activity. Therefore, a direct interaction of ACTH with SPM protein kinase(s) is likely to be responsible for its effect on phosphorylation.

Adenosine Triphosphate↗
PubMed1976

Interaction between ACTH fragments, brain opiate receptors and morphine-induced analgesia.

The present study confirms that N-terminal fragments of ACTH have an affinity for rat brain opiate receptors in vitro. Such peptides, devoid of corticotrophic activity, were found to inhibit morphine-induced analgesia if they also possessed affinity for opiate receptors in vitro. The structure-activity relationship for these two parameters is comparable to that observed for the same peptides on the induction of excessive grooming.

Adrenocorticotropic Hormone↗
PubMedDate not supplied

Characterization of beta-endorphin-immunoreactivity in limbic brain structures of rats self-administering heroin or cocaine.

The effects of intravenous self-administration of 30 micrograms infusions of either heroin or cocaine, or saline on the concentrations of beta-endorphin-immunoreactivity (beta E-IR) in the anterior part of the rat brain limbic system were studied. Self-administration of heroin and cocaine for 5 daily sessions resulted in a marked reduction of the concentrations of beta E-IR in the nucleus accumbens, rostral striatum, septum and hippocampus at the time of the scheduled next session on day 6. In pooled extracts of these regions from rats receiving saline, combined application of high-pressure liquid chromatography (HPLC) fractionation and specific radioimmunoassays revealed the presence of a number of beta E-related peptides co-chromatographing with synthetic non-acetylated and acetylated alpha, beta- and gamma-type endorphins. Similar profiles were found after HPLC fractionation of extracts of these regions from rats self-administering heroin and cocaine. Rats self-administering heroin or cocaine, however, showed decreased amounts of all detected forms of beta-endorphin as compared to saline rats. These findings indicate that both self-administration of an opiate that induces psychic as well as physical dependence and of a non-opiate stimulant inducing psychic but not physical dependence, results in a significant decrease of beta E and related peptides in limbic brain regions of the rat. All forms of beta E detected after HPLC were equally affected, suggesting an overall effect of the drugs on peptide turnover. These results suggest that beta E and related peptides may be involved in the neurochemical mechanisms underlying psychic dependence to drugs.

Animals↗
PubMedDate not supplied

Levels of CCK immunoreactivity and dopamine in the nucleus accumbens after 6-hydroxydopamine lesions of the ventral tegmental area and the nucleus accumbens.

The effects of 6-hydroxydopamine (6-OHDA) injected into either the ventral tegmental area (VTA) or the nucleus accumbens on dopamine and its metabolite DOPAC and CCK-immunoreactivity in the nucleus accumbens were studied. Measurements were made 1, 3 and 6 weeks after the lesion in both the anterior and posterior part of the nucleus accumbens. 6-OHDA applied in the VTA reduced the level of DA and DOPAC, but did not affect the CCK content in the nucleus accumbens. 6-OHDA lesions in the anterior part of the nucleus accumbens produced depletion of DA and DOPAC from one week after the injection, and decreased the CCK content 6 weeks after the injection. The results suggest that in the nucleus accumbens DA and CCK are localized, at least for the major part, in different nerve terminals.

3,4-Dihydroxyphenylacetic Acid↗
PubMedDate not supplied

Vasopressin(1-8) (des-glycinamide9-[Arg8]vasopressin) is an endogenous peptide present in rat plasma.

Using a radioimmunoassay for [Arg8]vasopressin(1-8) (des-glycinamide9-[Arg8]vasopressin; DGAVP) endogenous immunoreactive DGAVP (IR-DGAVP) was detected in extracts of plasma prepared from trunk blood of male Wistar rats. The IR-DGAVP was further characterized by reversed-phase high pressure liquid chromatography (HPLC). One of the two immunoreactive peaks obtained by HPLC coeluted with synthetic DGAVP and did not cross-react in a radioimmunoassay specific for [Arg8]vasopressin(1-9) (AVP). The other showed the chromatographical and radioimmunological characteristics of AVP. Analysis by HPLC of plasma prepared from fresh blood spiked with 3H-AVP indicated that under the experimental conditions employed no DGAVP was formed during extraction. The results indicate that DGAVP is present in rat plasma, possibly as an endogenous metabolite of AVP.

Animals↗