The effect of opiates on the activity of human placental aromatase/CYP19.

The effect of opiates on the activity of human placental aromatase/CYP19. Research Abstract Details 

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The effect of opiates on the activity of human placental aromatase/CYP19. Abstract Text:

Olga L Zharikova,Sujal V Deshmukh,Meena Kumar,Ricardo Vargas,Tatiana N Nanovskaya,Gary D V Hankins,Mahmoud S Ahmed,

Aromatase, cytochrome P450 19, is a key enzyme in the biosynthesis of estrogens by the human placenta. It is also the major placental enzyme that metabolizes the opiates L-acetylmethadol (LAAM), methadone, and buprenorphine (BUP). Methadone and BUP are used in treatment of the opiate addict and are competitive inhibitors of testosterone conversion to estradiol (E(2)) and 16alpha-hydroxytestosterone (16-OHT) to estriol (E(3)) by aromatase. The aim of this investigation is to determine the effect of 20 opiates, which can be administered to pregnant patients for therapeutic indications or abused, on E(2) and E(3) formation by placental aromatase. Data obtained indicated that the opiates increased, inhibited, or had no effect on aromatase activity. Their effect on E(3) formation was more pronounced than that on E(2) due to the lower affinity of 16-OHT than testosterone to aromatase. The K(i) values for the opiates that inhibited E(3) formation were sufentanil, 7 +/- 1 microM; LAAM, 13 +/- 8 microM; fentanyl, 25 +/- 5 microM; oxycodone, 92 +/- 22 microM; codeine, 218 +/- 69 microM; (+)-pentazocine, 225 +/- 73 microM. The agonists morphine, heroin, hydromorphone, oxymorphone, hydrocodone, propoxyphene, meperidine, levorphanol, dextrorphan, and (-)-pentazocine and the antagonists naloxone and naltrexone caused an increase in E(3) formation by 124-160% of control but had no effect on E(2) formation. Moreover, oxycodone and codeine did not inhibit E(2) formation and the IC(50) values for fentanyl, sufentanil, and (+)-pentazocine were >1000 microM. It is unlikely that the acute administration of the opiates that inhibit estrogen formation would affect maternal and/or neonatal outcome. However, the effects of abusing any of them during the entire pregnancy are unclear at this time.

The effect of opiates on the activity of human placental aromatase/CYP19. Publishing Authors By Initials

OL Zharikova,SV Deshmukh,M Kumar,R Vargas,TN Nanovskaya,GD Hankins,MS Ahmed,

For similar embryonic structures: placenta research abstracts see: embryonic structures: placenta research

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The effect of opiates on the activity of human placental aromatase/CYP19. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Biochemical pharmacology

VOLUME: 73

Page Numbers: 279-86

Journal Abbreviation: Biochem. Pharmacol.

ISSN: 0006-2952

DAY: 26

MONTH: 08

YEAR: 2006

The effect of opiates on the activity of human placental aromatase/CYP19. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 101032

The effect of opiates on the activity of human placental aromatase/CYP19. Keywords Mesh Terms:

KEYWORDS: Placenta

MESH TERMS: enzymology

Chemical & Substance for Abstract: The effect of opiates on the activity of human placental aromatase/CYP19. Information

Substance Name: Aromatase

Registry Number: EC 1.14.14.1

Grant and Affiliation Information for The effect of opiates on the activity of human placental aromatase/CYP19.

AFFILIATION: Department of Obstetrics and Gynecology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-0587, USA.

Country: England

AGENCY: United States NIDA

GRANT: DA13431

ACRONYM: DA

MEDLINETA: Biochem Pharmacol

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