Endogenous excitatory amino acids are involved in stress-induced adrenocorticotropin and catecholamine release.
The effect of N-methyl-D-aspartic acid (NMDA) receptor blockade on adrenocorticotropin (ACTH) and catecholamine activation during stress was investigated in conscious rats with indwelling catheters for both blood sampling and drug treatment. Secretion of ACTH in response to immobilization stress (20 min) was inhibited by pretreatment (20 min before stress exposure) with the centrally acting noncompetitive antagonist of NMDA receptors MK-801 (dizocilpine, the racemic form, 1 mg/kg i.p.) but not by 3-[(+/-)-2-carboxypiperazin-4-yl]propyl-1-phosphonic acid (CPP; 10 mg/kg i.p.), a competitive NMDA receptor antagonist. Administration of MK-801 (1 mg/kg i.p.) inhibited norepinephrine and totally prevented epinephrine response during acute immobilization stress. Pretreatment with a low dose of MK-801 (0.1 mg/kg i.p.) failed to modify basal or stress-induced ACTH and catecholamine release. The stress-induced rise in plasma epinephrine was found to be attenuated by the peripherally injected competitive antagonist CPP (10 mg/kg i.p.) suggesting that modulation not only of central but also of peripheral NMDA receptors may come into play. Our results indicate the involvement of endogenous excitatory amino acids in the control of ACTH and particularly of epinephrine secretion during stress.
Jezová
D
D
Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovakia.
Tokarev
D
D
Rusnák
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M
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D002395:Catecholamines / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004837:Epinephrine / Q000378:metabolism; D018846:Excitatory Amino Acids / Q000378:metabolism* / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D013312:Stress, Physiological; D013997:Time Factors
D002395:Catecholamines; D018846:Excitatory Amino Acids; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D000324:Adrenocorticotropic Hormone; D004837:Epinephrine