PMID- 9706478
OWN - NLM
STAT- MEDLINE
DCOM- 19981113
LR  - 20131121
IS  - 0258-851X (Print)
IS  - 0258-851X (Linking)
VI  - 12
IP  - 3
DP  - 1998 May-Jun
TI  - Is epinephrine-induced platelet aggregation autoregulated by its metabolic 
      degradation products in vivo?
PG  - 321-5
AB  - BACKGROUND: Catecholamines play an important role in platelet activation and 
      aggregation, epinephrine being the most potent one. Catecholamines are 
      substantially increased during stress, exercise or smoking and could result in 
      clinically important platelet activation if their action was not rapidly 
      regulated. In the present study the possible fast regulation of 
      epinephrine-induced platelet aggregation by its metabolic degradation products is 
      investigated. MATERIALS AND METHODS: Human platelet rich plasma (hPRP) and washed 
      rabbit platelets(wRP) were used for the study. The platelets irreversible 
      aggregation induced by epinephrine and ADP were monitored by an aggregometer 
      prior to and after the addition of the catecholamines degradation products 
      metanephrine, 3-methoxy-4-hydroxy-phenyl-glycole-aldehyde 
      (MHPGA),3-methoxy-4-hydroxy-phenyl-mandelic acid (VMA) 3,4-dihydroxy phenyl 
      glycole (DHPG),3,4-Dihydroxy-phenyl-glycole-aldehyde (DHPGA) and the 
      trimethoxy-phenyl-methyl-piperazine(TMP), a known free radical scavenger and 
      calcium antagonist. Linoleic acid-lipoxygenase reaction, in vitro was monitored 
      in the presence and absence of VMA. RESULTS: Metabolic degradation products 
      possessing a methoxy group at position 3 of the phenolic ring markedly inhibited 
      epinephrine and ADP-induced platelet aggregation at microM concentrations. The 
      most potent inhibitor of both agonists was metahephrine, followed by MHPGA and 
      VMA. TMZ also inhibited platelet aggregation at concentrations similar to VMA. 
      Dihydroxy-phenyl compounds failed to induce any inhibition. None of the 
      substances tested induced any aggregatory effect even at high concentrations (1 
      mM). VMA significantly inhibited linoleic acid-lipoxygenase reaction at 0.1 
      microM. CONCLUSIONS: Results indicate that catecholamines' degradation products 
      possessing methoxy (-OCH3) groups can rapidly inhibit in vitro and ex vivo 
      epinephrine-induced platelet aggregation. The inhibitory effects of methoxy 
      phenolic derivatives on epinephrine-induced platelet aggregation may possibly be 
      attributed to their free radical scavenging properties. There is substantial 
      evidence to conclude that an internal rapid autoregulation of epinephrine-induced 
      platelet aggregation, caused by its metabolic degradation products, takes place 
      in vivo.
FAU - Evangelou, A M
AU  - Evangelou AM
AD  - Laboratory of Experimental Physiology, University of Ioannina, Greece.
FAU - Malamas, M P
AU  - Malamas MP
FAU - Vezyraki, P
AU  - Vezyraki P
FAU - Karkabounas, S C
AU  - Karkabounas SC
LA  - eng
PT  - Journal Article
PL  - Greece
TA  - In Vivo
JT  - In vivo (Athens, Greece)
JID - 8806809
RN  - 0 (Platelet Aggregation Inhibitors)
RN  - 5001-33-2 (Metanephrine)
RN  - YKH834O4BH (Epinephrine)
SB  - IM
MH  - Animals
MH  - Epinephrine/metabolism/*pharmacology
MH  - *Homeostasis
MH  - Humans
MH  - Male
MH  - Metanephrine/pharmacology
MH  - Molecular Structure
MH  - Platelet Aggregation/*drug effects
MH  - Platelet Aggregation Inhibitors/pharmacology
MH  - Rabbits
EDAT- 1998/08/26 00:00
MHDA- 1998/08/26 00:01
CRDT- 1998/08/26 00:00
PHST- 1998/08/26 00:00 [pubmed]
PHST- 1998/08/26 00:01 [medline]
PHST- 1998/08/26 00:00 [entrez]
PST - ppublish
SO  - In Vivo. 1998 May-Jun;12(3):321-5.