Differential effects of protein kinase C activation on catecholamine secretions evoked by stimulations of various receptors in the rat adrenal medulla

Warashina, Akira; Fujiwara, Naoshi

doi:10.1016/0304-3940(91)90456-4

Cited by 8 publications

(3 citation statements)

References 17 publications

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“…2e-h). Previous studies showed that the nonphorbol PKC activator mezerein also modulated secretory responses evoked by these secretagogues in manners similar to those shown with PDBu [6,19], and a phorbol ester ineffective in activating PKC did not affect secretory responses [6]. Moreover, the PKC inhibitor Ro 31-8220 antagonized the inhibitory effect of PDBu on histamine-evoked secretion [14].…”

Section: Differential Modulation Of Secretory Responses Evoked By Varmentioning

confidence: 95%

“…In intact chromaffin cells, a variety of effects of phorbol esters on stimulant-evoked secretory responses have been reported. The treatment of the rat adrenal medulla with phorbol esters increased CA secretions evoked by nicotine [4], high K + [4,5] or bradykinin [6], but inhibited those evoked by muscarinic agents or histamine [5,6]. Thus, the mode of modulation of secretory responses following activation of PKC seems to depend on secretagogues used for stimulation.…”

Section: Introductionmentioning

confidence: 96%

“…In the previous study [14], the homologous desensitization of histamineevoked secretion was shown to be mediated, at least in part, by the activation of PKC after H 1 receptor stimulation. Moreover, crosscommunications among various receptors in the modulation of secretory responses in rat chromaffin cells have been demonstrated [5,6,10]. The role of such modulations in controlling CA secretion in the adrenal medulla in physiologic conditions remains to be studied.…”

Section: Modulations Of Secretory Responses Bymentioning

confidence: 99%

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Modulations of Early and Late Secretory Processes by Activation of Protein Kinases in the Rat Adrenal Medulla

Warashina¹

1998

Neurosignals

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Modulatory effects of the activation of either protein kinase C (PKC) by phorbol 12,13-dibutyrate (PDBu) or protein kinase A (PKA) by forskolin on stimulant-evoked secretory processes in the perfused rat adrenal medulla were studied. PDBu or forskolin was applied during repetitive stimulation (30 s each at 10-min intervals) with nicotine, bradykinin, muscarine or histamine, and changes in [Ca²⁺]_i (fura-2 microfluorometry) and catecholamine secretions (electrochemical detection) were simultaneously measured. PDBu markedly potentiated the nicotine-evoked secretion without altering the [Ca²⁺]_i response. PDBu partially inhibited the muscarine-evoked secretion and almost completely blocked the histamine-evoked secretion, concomitantly with extensive suppressions of the [Ca²⁺]_i responses to these stimulants. The bradykinin-evoked secretion was enhanced by PDBu despite a slight attenuation of the [Ca²⁺]_i response. PDBu reduced bradykinin-induced intracellular Ca²⁺ release in a Ca²⁺-free medium but enhanced the secretion associated with the released Ca²⁺. These results suggest that PDBu-activated PKC modulates secretory processes at, at least, two different stages. An early-stage modulation may downregulate receptor/G protein systems, which accounts for the inhibitory effect of PDBu on the muscarine- and histamine-evoked responses. A late-stage modulation may generally promote Ca²⁺-triggered exocytosis after elevation of [Ca²⁺]_i, which explains the potentiation of the nicotine-evoked secretion by PDBu. The late-stage modulation may counteract the early-stage modulation in bradykinin-stimulated cells. Forskolin potentiated the secretory responses to the four secretagogues without increasing the [Ca²⁺]_i responses. PKA may modulate secretory process at a step(s) distal to the rise in [Ca²⁺]_i as is the case with the late-stage modulation by PKC.