Inhibition by yohimbine of the calcium-dependent evoked release of [3H]GABA in rat and mouse brain slices in vitro.
Calcium-dependent release of [3H]GABA was elicited by electrical stimulation in slices of rat and mouse cerebral cortex or by potassium stimulation in the mouse brain-stem. The stimulation-evoked release of [3H]GABA was inhibited by yohimbine in a concentration-dependent manner. High concentrations of other alpha-adrenoceptor antagonists such as phentolamine, RS 21361, idazoxan, rauwolscine and corynanthine also inhibited [3H]GABA release. This effect was not observed with pseudoyohimbine or prazosin. [3H]GABA release was not affected by exposure to the alpha-adrenoceptor agonists clonidine, M7, noradrenaline or methoxamine. In addition, clonidine did not antagonize the yohimbine-induced inhibition of [3H]GABA release. The inhibitory effect of yohimbine did not result from an interaction with endogenously released noradrenaline since the inhibition was still observed in reserpine-pretreated animals. It is concluded that yohimbine and other alpha 2-adrenoceptor antagonists inhibit the stimulation-evoked release of [3H]GABA through a mechanism which appears to be independent of the blockade of alpha 2-adrenoceptors and which does not involve an interaction with endogenous noradrenaline. The present results indicate that yohimbine exerts non-specific actions on the release of [3H]GABA and that similar effects can be observed with other alpha-adrenoceptor blocking agents in high concentrations. Consequently, when studying the effects of yohimbine and other alpha 2-adrenoceptor antagonists on noradrenergic neurotransmission, the possibility of non-specific effects should be taken into consideration, particularly in the high concentrations range.
Maurin
Y
Y
Arbilla
S
S
Langer
S Z
SZ
D000818:Animals; D001921:Brain / Q000378:metabolism*; D001933:Brain Stem / Q000378:metabolism; D002118:Calcium / Q000037:antagonists & inhibitors*; D002540:Cerebral Cortex / Q000378:metabolism; D004558:Electric Stimulation; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009638:Norepinephrine / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D012636:Secretory Rate / Q000187:drug effects; D013237:Stereoisomerism; D015016:Yohimbine / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D005680:gamma-Aminobutyric Acid; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine