DOPA Potentiation by a hypothalamic factor, MSH release-inhibiting hormone (MIF)

Plotnikoff, Nicholas P.; Kastin, Abba J.; Anderson, Mary B.; Schally, Andrew V.

doi:10.1016/0024-3205(71)90326-2

Cited by 184 publications

(24 citation statements)

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“…Behavioral tests of the increase in the effects of DOPA and pargyline were conducted in the Everett DOPA potentiation test, as previously reported [Plotnikoff et at.. 1971]. The critical variable in the DOPA test is the dose of pargyline (from 40 to 50 mg/kg) which depends on the age and strain of rodent employed.…”

Section: Methodsmentioning

confidence: 99%

DOPA Potentiation in Ablated Animals and Brain Levels of Biogenic Amines in Intact Animals after Prolyl-leucylglycinamide

Plotnikoff¹,

Minard²,

Kastin³

1974

Neuroendocrinology

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Prolyl-leucylglycinamide (PLG) wasfound to augment the behavioral effects of DOPA and pargyline in mice and rats when administered orally. Behavioral studies in the DOPA test with repeated doses of PLG over 5 days did not reveal either cumulative or tolerance effects. Ablation of the pituitary, adrenals, ovaries, testes, pineal, spleen, thyroid, parathyroid, one kidney, or thymus did not disrupt this behavioral potentiation of DOPA by PLG. Furthermore, a neurochemical study in mice and rats did not show any significant increase in the content of dopamine, norepinephrine, or serotonin in the mouse brain. These studies suggest that PLG may have direct stimulatory effects on the mouse brain which do not require the presence of a number of somatic organs.

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Section: Methodsmentioning

confidence: 99%

DOPA Potentiation in Ablated Animals and Brain Levels of Biogenic Amines in Intact Animals after Prolyl-leucylglycinamide

Plotnikoff¹,

Minard²,

Kastin³

1974

Neuroendocrinology

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“…Enhanced locomotor activity following monoamine oxidase inhibition plus L-DOPA administration is seen if the animals have been pretreated with either of the peptides thyrotropin releasing hormone (TRH) or melanocyte stimulating hormone release inhibitory factor (MIF) (Plotnikoff, Kastin, Anderson & Schally, 1971;Plotnikoff, Prange, Breese, Anderson & Wilson, 1972; Plotnikoff, Prange, Breese & Wilson, 1974;Green & Grahame-Smith, 1974a; Huidobro-Toro, Scotti de Carolis & Longo, 1974).…”

Section: Introductionmentioning

confidence: 99%

EVIDENCE CONCERNING THE INVOLVEMENT OF 5‐HYDROXYTRYPTAMINE IN THE LOCOMOTOR ACTIVITY PRODUCED BY AMPHETAMINE OR TRANYLCYPROMINE PLUS l‐DOPA

Green¹,

Kelly

1976

British J Pharmacology

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I Pretreatment of rats with p-chlorophenylalanine (PCPA; 2 x 200 mg/kg) decreased the concentration of 5-hydroxytryptamine (5-HT) in the brain. It also decreased the locomotor activity produced by tranylcypromine plus L-DOPA administration 24 h after the second dose of PCPA. 2 Pretreatment with p-chloroamphetamine, which produced a similar decrease in brain 5-HT concentrations did not decrease the locomotor response to tranylcypromine and L-DOPA. 3 PCPA pretreatment decreased the rise in the concentration of DOPA and dopamine in the brain following tranylcypromine and L-DOPA, suggesting its effect on the dopamine-induced locomotor activity was the result of this drug diminishing dopamine formation in the brain, probably by inhibiting L-DOPA uptake. 4 The locomotor activity produced by tranylcypromine and L-DOPA was not decreased by pretreatment 6 h earlier with disulfiram (400 mg/kg). This argues against the locomotor activity being due to noradrenergic stimulation. 5PCPA pretreatment did not alter amphetamine-induced stereotypy or the circling behaviour in unilateral nigro-striatal lesioned rats.

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Section: Introductionmentioning

confidence: 99%

“…Several years ago it was proposed that the hypothalamic factor Pro-Leu-Gly-NH2, enzymatically derived from its prohormone oxytocin, is an inhibiting factor for the release of pituitary melanotropin (melanocyte-stimulating hormone, MSH) (1). This biologically active tripeptide was subsequently isolated from bovine pituitary extracts (2) and it has since been found to possess additional, extrapituitary activities (3,4).On the basis of 1H nuclear magnetic resonance in dimethylsulfoxide and preliminary crystallographic data, Walter et al proposed a preferred conformation of Pro-Leu-Gly-NH2, consisting of a 10-membered fl-turn (4 -1) closed by a hydrogen bond (5). This structure was confirmed by the x-ray crystallographic study of Reed and Johnson (6).…”

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Theoretical studies on pro-leu-gly-nh2 conformation.

Kang¹,

Walter²

1976

Proc. Natl. Acad. Sci. U.S.A.

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Classical potential function calculations were carried out on the hypothalamic factor Pro-Leu-Gly-NH2. The results indicate that the proposed 1O-membered, hydrogen-bonded f-turn conformation of this tripeptide is a strongly preferred structure. Its stability appears to be inherent in the rather rigid backbone conformation of the leucine residue rather than the hydrogen bond between the carboxamide proton of glycinamide and the C=O of the proline moiety; the glycinamide has little influence on the 04 of the leucine backbone structure. The type II Mturn structure of the Pro-Leu-Gly-NH2 is preferred. Several years ago it was proposed that the hypothalamic factor Pro-Leu-Gly-NH2, enzymatically derived from its prohormone oxytocin, is an inhibiting factor for the release of pituitary melanotropin (melanocyte-stimulating hormone, MSH) (1). This biologically active tripeptide was subsequently isolated from bovine pituitary extracts (2) and it has since been found to possess additional, extrapituitary activities (3,4).On the basis of 1H nuclear magnetic resonance in dimethylsulfoxide and preliminary crystallographic data, Walter et al. proposed a preferred conformation of Pro-Leu-Gly-NH2, consisting of a 10-membered fl-turn (4 -1) closed by a hydrogen bond (5). This structure was confirmed by the x-ray crystallographic study of Reed and Johnson (6). Measurements of spin-lattice relaxation times of the carbon-13 nuclei of Pro-Leu-Gly-NH2 by Deslauriers et al. (7) showed this tripeptide to have a compact but flexible structure in aqueous medium. In addition, classical potential function calculations which incorporated electrostatic, torsion, and hydrogen-bond contributions revealed a large number of preferred conformations including the 4 -1 fl-turn (8).The present conformational energy calculations using the classical Lennard-Jones potential function, which includes an electrostatic term, represent a further attempt to ascertain whether the stability of the proposed structure of ProLeu-Gly-NH2 is primarily due to the hydrogen bonding energy or is actually inherent in the backbone of this tripeptide. A second goal of this study was to determine whether there was a preference for one of the two theoretically possible types of f-turn conformations (9-12). One is the type I, in which the leucine side chain would occupy an axial position, and the other is the type II with an equatorial position of the leucine side chain. Knowledge of the preferred type of f-turn of Pro-Leu-Gly-NH2 may be of particular interest when one considers the biological activity of this hypothalamic factor and its analogs. METHODS The Lennard-Jones 6-12 potential function was used, including an electrostatic term, and the procedure has been described in detail (13). The net charges in the Coulomb term were calculated by the INDO molecular orbital method. The molecular geometry of Pro-Leu-Gly-NH2 (Fig. 1) has been constructed using the reported x-ray crystallographic data (6) with the naturally occurring Pro(S)-Leu(S) absolute configuration. The...

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DOPA Potentiation by a hypothalamic factor, MSH release-inhibiting hormone (MIF)

Cited by 184 publications

References 11 publications

DOPA Potentiation in Ablated Animals and Brain Levels of Biogenic Amines in Intact Animals after Prolyl-leucylglycinamide

DOPA Potentiation in Ablated Animals and Brain Levels of Biogenic Amines in Intact Animals after Prolyl-leucylglycinamide

EVIDENCE CONCERNING THE INVOLVEMENT OF 5‐HYDROXYTRYPTAMINE IN THE LOCOMOTOR ACTIVITY PRODUCED BY AMPHETAMINE OR TRANYLCYPROMINE PLUS l‐DOPA

Theoretical studies on pro-leu-gly-nh2 conformation.

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