Use of Parenteral Dipeptides To Increase Serum Tyrosine Levels and To Enhance Catecholamine-Mediated Neurotransmission

The use of intravascular tyrosine (TYR) to enhance catecholamine release in hemorrhagic shock and other cardiovascular diseases, or as a constituent of nutrient mixtures used for total parenteral nutrition, is limited by the unusually poor solubility of the amino acid in water. We have thus examined...

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Bibliographic Details
Published in:Journal of pharmaceutical sciences 1990-08, Vol.79 (8), p.685-687
Main Authors: Maher, Timoth J., Kiritsy, Paul J., Moya-Huff, Fernando A., Casacci, Franco, De Marchi, Franco, Wurtman, Richard J.
Format: Article
Language:English
Subjects:
Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
Animals
Biological and medical sciences
Blood Pressure - drug effects
Catecholamines - physiology
Dipeptides - pharmacokinetics
Dipeptides - pharmacology
Emergency and intensive care: metabolism and nutrition disorders. Enteral and parenteral nutrition
Hemodynamics - drug effects
Hypotension - physiopathology
Intensive care medicine
Male
Medical sciences
Rats
Rats, Inbred SHR
Rats, Inbred Strains
Space life sciences
Synaptic Transmission - drug effects
Tyrosine - blood
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Summary:The use of intravascular tyrosine (TYR) to enhance catecholamine release in hemorrhagic shock and other cardiovascular diseases, or as a constituent of nutrient mixtures used for total parenteral nutrition, is limited by the unusually poor solubility of the amino acid in water. We have thus examined the ability of various TYR‐containing dipeptides, which are more water soluble than the amino acid, to raise serum TYR, to restore blood pressure in hemorrhaged hypotensive rats, and to lower blood pressure in spontaneously hypertensive rats (SHR). L‐Tyrosyl‐L‐proline (TYR‐PRO), L‐tyrosyl‐L‐alanine (TYR‐ALA), L‐alanyl‐L‐tyrosine (ALA‐TYR), and L‐tyrosyl‐L‐tyrosine (TYR‐TYR) given intravenously (12.5–25 mg/kg) all caused significant increases in serum TYR; the increase after TYR‐PRO was dose related in the range 12.5–50 mg/kg. All of the dipeptides also caused significant elevations in blood pressure among hypotensive rats when administered intraarterially. Moreover, given intraperitoneally (100 mg/kg), all of them also lowered blood pressure in SHRs. These observations suggest that TYR‐containing dipeptides may be useful in some clinical situations where maintaining or elevating blood TYR levels would be desirable.
ISSN:0022-3549
1520-6017
DOI:10.1002/jps.2600790807