Facilitation of noradrenaline release from rat brain slices by beta-adrenoceptors.
The present study examined whether stimulation of beta-adrenoceptors facilitated noradrenaline release in the rat brain. Electrical stimulation-evoked overflow of tritium from rat cerebral cortical, hypothalamic and hippocampal slices labelled with 3H-noradrenaline was measured during superfusion for 100 min. Tissue slices were electrically simulated (1 Hz, 20 mA, 2 ms, 2 min), at 20 (S1) and 70 (S2) min after the onset of superfusion. The nonselective beta-adrenoceptor agonist isoproterenol (0.1-10 nM) enhanced stimulation-evoked overflow of tritium from slices of cerebral cortex, hypothalamus and hippocampus in a concentration-dependent manner; mean S2/S1 ratios with 10 nM isoproterenol were 161 +/- 11%, 142 +/- 15% and 143 +/- 12% of control, respectively, in the three brain regions. The facilitatory effect of isoproterenol in cerebral cortical slices was antagonized by propranolol (50 nM), a nonselective beta-adrenoceptor antagonist, and by the beta 1- and beta 2-selective adrenoceptor antagonists ICI 89,406 (1 nM) and ICI 118,551 (1 nM), respectively. The beta 1- and beta 2-selective adrenoceptor agonists prenalterol and albuterol (0.1-10 nM), respectively, also increased stimulation-evoked overflow of tritium from cerebral cortical slices; these effects were antagonized by beta-adrenoceptor antagonists. These findings suggest that stimulation of beta-adrenoceptors enhance noradrenaline release from rat cerebral cortical, hypothalamic and hippocampal slices; this release mechanism appears to involve both beta 1- and beta 2-adrenoceptor subtypes. These facilitating presynaptic receptors may be involved in mediating the antidepressant-like behavioral effects of beta 2-adrenoceptor agonists.
Murugaiah
K D
KD
Department of Pharmacology and Therapeutics, Louisiana State University Medical School Shreveport 71130-3932, USA.
O'Donnell
J M
JM
D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006624:Hippocampus / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D011294:Prenalterol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D011943:Receptors, Adrenergic, beta; D007545:Isoproterenol; D011294:Prenalterol; D000420:Albuterol; D009638:Norepinephrine