Article date: March 1991
By: Judit Mally, J.H. Connick, T.W. Stone, in Volume 102, Issue 3, pages 711-717
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.
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 μm) was shared by (+)‐isoprenaline at the much higher concentration of 10 μm.
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.
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.
Propranolol superfusion blocked responses to both isomers of isoprenaline and 5‐HT but did not affect sensitivity to adenosine.
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.
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.
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.
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 μm) was shared by (+)‐isoprenaline at the much higher concentration of 10 μm.
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.
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.
Propranolol superfusion blocked responses to both isomers of isoprenaline and 5‐HT but did not affect sensitivity to adenosine.
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.
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.
DOI: 10.1111/j.1476-5381.1991.tb12238.x
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