Inability to condition a peripheral activating drug

Previous research on the adaptation of the conditional renal secretion reflex (CR) has resulted in contradictory data. Although the early work of Bykov in Russia on dogs and of Hoferet al. in the United States on humans indicated that a renal CR is possible, experiments of Corson, Reese and Dykman (in normal dogs) and of Frances Watt Baker and Gantt (in dogs with transplanted kidneys) showed little or no capacity for forming a renal CR. The present work is a partial completion of a comprehensive survey of the ability and mechanism of the kidneys to form CRs. The production of glycosuria produced byperipheral stimulation cannot be conditioned. The results of 110 days of experiments with an externalized ureter dog injected with 2.5 mg of phloridzin (im) in 0.5 ml of normal saline were: 0.40 mg, 0.43 mg (control before phloridzin injection), 0.96, 8.71, 10.96, 7.28 and 4.36 mg glucose. On the test days an equal amount of normal saline was injected with the following results: 0.29, 0.38 mg glucose (control), 0.33, 0.45, 0.38, 0.32 and 0.35 mg. All readings are glucose per minute, average of 10 experiments for each of the above readings. The results of 75 days of experiments with the cervical kidney dog injected with the same amount of phloridzin as above in normal saline were: 0.29, 0.37 mg glucose/min (control), 1.72, 4.56, 5.43, 3.92 and 2.54 mg glucose/min (after phloridzin). On test days an equal amount of saline was injected, results: 0.27, 0.28 mg (control), 0.25, 0.29, 0.36, 0.26 and 0.29 mg of glucose/min, average of 10 experiments for each of the above readings. All figures are for 15 minute collections. Conclusion: Glycosuria produced by tubular inhibition (phloridzin) cannot become a conditional response. One explanation of this failure to form a CR is that phloridzin acts peripherally rather than centrally.