Changes in neurotransmitter sensitivity in the mouse neocortical slice following propranolol and theophylline administration.
1. The mouse neocortical slice has been used to examine the sensitivity of neurones to isoprenaline, 5-hydroxytryptamine (5-HT) and adenosine acutely and following chronic treatment of animals with propranolol or theophylline. 2. While having little effect alone, all three agonists enhanced the d.c. depolarizing potential produced by N-methyl-D-aspartate (NMDA). The effect of (-)-isoprenaline (0.2 microM) was shared by (+)-isoprenaline at the much higher concentration of 10 microM. 3. Superfusion of slices with theophylline or 8-phenyltheophylline blocked responses to adenosine with evidence of selectivity. A single injection of theophylline 24 h before slice preparation did not alter agonist sensitivity, but when administered daily at 100 mg kg-1 for 14 days, the xanthine caused a loss of sensitivity to adenosine and (-)-isoprenaline but not 5-HT. The lower dose of theophylline, 10 mg kg-1 daily, also led to a loss of adenosine responses but no change of sensitivity to the amines. 4. Following the 14 day treatment with theophylline at 100 mg kg-1 daily in two groups of mice, responses to adenosine recovered to control levels after 20 days. 5. Propranolol superfusion blocked responses to both isomers of isoprenaline and 5-HT but did not affect sensitivity to adenosine. 6. Chronic treatment with propranolol at 25 mg kg-1 daily for 14 days induced a loss of sensitivity to (-)-isoprenaline and 5-HT but not adenosine. A lower dose of 5 mg kg-1 daily caused no change in responses to adenosine or 5-HT, but yielded an increased sensitivity to (-)-isoprenaline. 7. The results are discussed with respect to reports of receptor up-regulation in binding studies; caution is clearly required in extrapolating from such work to receptor activity in a functional system, especially in the case of theophylline and adenosine.
Mally
J
J
Department of Pharmacology, University of Glasgow.
Connick
J H
JH
Stone
T W
TW
D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D051379:Mice; D016202:N-Methylaspartate / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology*; D012701:Serotonin / Q000494:pharmacology; D013806:Theophylline / Q000494:pharmacology*
D012701:Serotonin; D016202:N-Methylaspartate; D011433:Propranolol; D013806:Theophylline; D000241:Adenosine; D007545:Isoproterenol