The effects of D-phenylalanine and its derivatives on enkephalin degradation in vitro: Relation to analgesia and attenuation of the morphine withdrawal syndrome

P. K. Janicki, S. W. Gumułka, Z. Szreniawski, E. A. Paulo, Z. Arnold

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Abstract

The effect of D-Phenylalanine (D-Phe), a putative carboxypeptidase A inhibitor and its four derivatives (T1-T4) on analgesia, development of tolerance and physical dependence to morphine, and on degradation of both exogenous and endogenous enkephalins was investigated. Systemic administration of either D-Phe or its derivatives produced naloxone-reversible analgesia in the hot-plate test in mice. Naloxone-precipitated morphine withdrawal syndrome was attenuated in mice after systemic subacute administration (7 days, 1.2 mmol/kg, sc) of D-phe derivatives, the development of tolerance to morphine being unchanged. In the presence of either D-Phe or its derivatives in an incubation mixture (up to 10-3 mol/l) the hydrolysis of exogenous 3H-Met5- and 3H-Leu5-enkephalin in striatal homogenates was slightly inhibited. Moreover, the addition of D-Phe or its derivatives seemed to increase the per cent of recovered endogenous Met5-enkephalin released from veratridine-depolarized striatal particles. In contrast, bestatin, an amino-peptidase inhibitor, and a mixture of dipeptides (Tyr-Tyr, Leu-Leu, Leu-Gly) markedly inhibited degradation of both endogenous and exogenous enkephalins in vitro. The results obtained in this study suggest that the pharmacological activity of D-Phe is not directly related to the endogenous opiate system.

Original languageEnglish (US)
Pages (from-to)41-49
Number of pages9
JournalPolish Journal of Pharmacology and Pharmacy
Volume38
Issue number1
StatePublished - Dec 1 1986

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Enkephalins
Phenylalanine
Analgesia
Morphine
Corpus Striatum
Naloxone
tyrosyltyrosine
glycylleucine
leucylleucine
Morphine Dependence
Carboxypeptidases A
Veratridine
Opioid Peptides
Dipeptides
Protease Inhibitors
Hydrolysis
In Vitro Techniques
Pharmacology

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science

Cite this

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abstract = "The effect of D-Phenylalanine (D-Phe), a putative carboxypeptidase A inhibitor and its four derivatives (T1-T4) on analgesia, development of tolerance and physical dependence to morphine, and on degradation of both exogenous and endogenous enkephalins was investigated. Systemic administration of either D-Phe or its derivatives produced naloxone-reversible analgesia in the hot-plate test in mice. Naloxone-precipitated morphine withdrawal syndrome was attenuated in mice after systemic subacute administration (7 days, 1.2 mmol/kg, sc) of D-phe derivatives, the development of tolerance to morphine being unchanged. In the presence of either D-Phe or its derivatives in an incubation mixture (up to 10-3 mol/l) the hydrolysis of exogenous 3H-Met5- and 3H-Leu5-enkephalin in striatal homogenates was slightly inhibited. Moreover, the addition of D-Phe or its derivatives seemed to increase the per cent of recovered endogenous Met5-enkephalin released from veratridine-depolarized striatal particles. In contrast, bestatin, an amino-peptidase inhibitor, and a mixture of dipeptides (Tyr-Tyr, Leu-Leu, Leu-Gly) markedly inhibited degradation of both endogenous and exogenous enkephalins in vitro. The results obtained in this study suggest that the pharmacological activity of D-Phe is not directly related to the endogenous opiate system.",
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The effects of D-phenylalanine and its derivatives on enkephalin degradation in vitro : Relation to analgesia and attenuation of the morphine withdrawal syndrome. / Janicki, P. K.; Gumułka, S. W.; Szreniawski, Z.; Paulo, E. A.; Arnold, Z.

In: Polish Journal of Pharmacology and Pharmacy, Vol. 38, No. 1, 01.12.1986, p. 41-49.

Research output: Contribution to journalArticle

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T1 - The effects of D-phenylalanine and its derivatives on enkephalin degradation in vitro

T2 - Relation to analgesia and attenuation of the morphine withdrawal syndrome

AU - Janicki, P. K.

AU - Gumułka, S. W.

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AU - Arnold, Z.

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