A multi-chamber perifusion system, capable of detecting transient secretory events, was used to define the roles of stepwise changes and gradients of K+ concentration in modulation of α-MSH and endorphin secretion. Fifteen dispersed mouse neuro-intermediate lobes per chamber were peri fused with Dulbecco's Modified Eagle Medium at 0.5 ml/min. One-min fractions were collected. Ten min of 67 mM K+ elicited an immediate, very brief 4-fold increase in secretion of both hormones. Surprisingly, the return to normal K+ elicited a similar increase in secretion. Ten min K+-free medium produced an immediate decrease in secretion. Exposure to a 10-min 0-67 mM K+ gradient did not produce an increase in secretion; however, the Stepwise return to normal K+, identical to that in the first experiment, elicited an immediate, brief increase in secretion. Conclusions: 1) The rapid decline in secretory activity during 67 mM K+ cannot be explained either by “down regulation” of receptors, since t h i s secretagogue is not receptor-mediated, or by depletion of labile hormone, since a second secretory episode occurred immediately following termination of high K+. This suggests that some other cellular mechanism “uncouples” stimulus-secretory mechanisms. 2) Although depolarization with high K+ and hyperpolarization with K+-free medium were associated with increases and decreases, respectively, in secretion, i t appears that i t is the rate of ion flux rather than polarization which is responsible for stimulus-secretion coupling.
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