Acute and chronic effects of reserpine on biochemical and functional parameters of central and peripheral alpha 2-adrenoceptors.
The specific binding of the agonist, [3H]UK 14304, and of the antagonist, [3H]RX 821002, to rat brain membranes, as well as clonidine-induced mydriasis, clonidine-induced inhibition and idazoxan-induced stimulation of brain 3,4-dihydroxyphenylalanine (DOPA) synthesis, and clonidine and UK 14304-induced inhibition of twitch responses in the vas deferens were used to evaluate the affinity and sensitivity of central and peripheral alpha 2-adrenoceptors after various treatments with reserpine. Treatment with reserpine (0.25 mg/kg s.c., every 48 h) for 4, 11 and 18 days induced consistent and significant increases in the affinity (KD values) of [3H]UK 14304 for the cortical alpha 2-adrenoceptor with no change in receptor density. Chronic treatment with reserpine also resulted in a greater affinity of (-)-adrenaline for the high-affinity state of the alpha 2-adrenoceptor when the catecholamine competed with the binding of [3H]RX 821002 to cortical membranes. In line with these radioligand binding data, various functional responses mediated by central and peripheral alpha 2-adrenoceptors were found to be potentiated after repeated treatment with reserpine. Thus, the inhibitory alpha 2-autoreceptor that modulates the synthesis of brain noradrenaline and the central postsynaptic inhibitory alpha 2-adrenoceptor that induces mydriasis displayed greater responses in vivo after chronic treatment with reserpine. Short-term and chronic treatments with reserpine also increased the sensitivity of peripheral presynaptic alpha 2-adrenoceptors in the vas deferens.(ABSTRACT TRUNCATED AT 250 WORDS)
Ugedo
L
L
Department of Pharmacology, Faculty of Medicine, University of the Basque Country, Leioa, Bizkaia, Spain.
Garro
M A
MA
Pineda
J
J
Giralt
M T
MT
Miralles
A
A
Olmos
G
G
García-Sevilla
J A
JA
Menargues
A
A
Obach
R
R
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D000068438:Brimonidine Tartrate; D003000:Clonidine / Q000494:pharmacology; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D004146:Dioxanes / Q000378:metabolism / Q000494:pharmacology; D019329:Idazoxan / Q000031:analogs & derivatives; D007279:Injections, Subcutaneous; D008297:Male; D015878:Mydriasis / Q000139:chemically induced; D011810:Quinoxalines / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000378:metabolism; D012110:Reserpine / Q000494:pharmacology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D014649:Vas Deferens / Q000187:drug effects / Q000294:innervation / Q000502:physiology
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D011810:Quinoxalines; D011942:Receptors, Adrenergic, alpha; D000068438:Brimonidine Tartrate; D004295:Dihydroxyphenylalanine; D012110:Reserpine; C058525:2-methoxyidazoxan; D014446:Tyrosine 3-Monooxygenase; D003000:Clonidine; D019329:Idazoxan