Effects of MPP+ on catecholamine levels in adrenal glands and heart of rats.
The effects of MPP+ (2.5-20 mg/kg) on the adrenal glands and heart were investigated in rats. At various periods after s.c. drug administration the rats were decapitated and tissue catecholamine levels were determined by means of HPLC with electrochemical detection. Adrenal dopamine (DA) levels were reduced at 2-8 h after MPP+ administration, but this decrease was followed by an elevation after 16 h and return to the control values after one week. Three successive injections of MPP+ caused a statistically significant elevation in adrenal DA, one day, with a tendency to elevation four and seven days after the last injection, whereas a severe (up to 96%) decrease in heart noradrenaline (NA) was found one day after the last injection. Seven days after the last injection a 50% depletion of NA in the heart was still observed. Pretreatment with GBR 12909 (30 mg/kg, 4h) blocked the MPP+ (10 mg/kg, 2 h) induced reduction of adrenal DA levels, but at the same time GBR 12909 failed to block the effects of MPP+ in the heart. One day after three successive daily injections of MPP+ (10 mg/kg each), the DA-uptake inhibitor GBR 12909 (30 mg/kg, 6 h) could still induce an increase in adrenal DA. MPP+ appears to lack persistent cytotoxic action in the adrenal medulla but rather to cause a transient inhibition of DA synthesis followed by a compensatory stimulation. The inhibition can be blocked by specific inhibitor of the DA-uptake mechanism, suggesting a direct effect of MPP+ taken up by adrenomedullary cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Kujacic
M
M
Department of Pharmacology, University of Göteborg, Sweden.
Carlsson
A
A
D015655:1-Methyl-4-phenylpyridinium / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000633:toxicity; D000313:Adrenal Medulla / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism*; D002396:Catechols / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006321:Heart / Q000187:drug effects* / Q000294:innervation; D007279:Injections, Subcutaneous; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009206:Myocardium / Q000378:metabolism*; D009419:Nerve Tissue Proteins; D010879:Piperazines / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D002352:Carrier Proteins; D002395:Catecholamines; D002396:Catechols; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D010879:Piperazines; C043425:vanoxerine; C034221:catechol; D015655:1-Methyl-4-phenylpyridinium