Effects of thyroid hormone deficiency on pre- and postsynaptic noradrenergic mechanisms in the rat cerebral cortex.
Thyroid hormones are known to influence the noradrenergic neurotransmission in several peripheral organs. In order to find out whether similar changes exist in the central nervous system, we investigated adrenoceptor-mediated responses in the rat brain cortex during propylthiouracil-induced hypothyroidism. In contrast to unchanged basal cAMP levels, the cAMP accumulation following (-)noradrenaline incubation (3 X 10(-6)--3 X 10(-5) M) was significantly reduced in brain slices from hypothyroid animals. The difference between controls and propylthiouracil-fed rats became more pronounced when (-) isoprenaline (3 X 10(-6)--3 X 10(-5) M) was used for selective stimulation of beta-adrenoceptors. Since the cAMP increase mediated via alpha-adrenoceptors was not affected, it may be concluded that thyroid hormone deficiency only impairs the beta-adrenergic transmission. Phosphodiesterase activity remained unaltered suggesting that thyroid hormones influence the beta-adrenoceptors or the adenylate cyclase coupled to it. The sensitivity of presynaptic alpha-adrenoceptors modulating the release of noradrenaline was evaluated using occipital cortical slices preincubated in 3H-noradrenaline. Clonidine inhibited whereas phentolamine enhanced the 3H-overflow induced by electrical stimulation in a dose-dependent manner. No differences could be detected between control- and propylthiouracil-treated animals. Thus presynaptic alpha-adrenoceptors are not affected by hypothyroidism.
D000818:Animals; D002540:Cerebral Cortex / Q000201:enzymology / Q000378:metabolism*; D003000:Clonidine / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007037:Hypothyroidism / Q000139:chemically induced / Q000378:metabolism*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D011441:Propylthiouracil; D051381:Rats; D011941:Receptors, Adrenergic / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*
D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D011441:Propylthiouracil; D000242:Cyclic AMP; D010727:Phosphoric Diester Hydrolases; D007545:Isoproterenol; D003000:Clonidine; D009638:Norepinephrine; D010646:Phentolamine