Forskolin, a tool for rat parotid secretion studies: 45Ca efflux is not related to cAMP

Abstract

In the present work, we investigated, by use of forskolin, whether adenosine 3',5'-cyclic monophosphate (cAMP) level and Ca movements were modulated sequentially or in parallel by the activation of the beta-adrenergic receptor in the rat parotid gland. Forskolin-induced [3H]protein secretion was dependent on external Ca, whereas isoproterenol-induced secretion was not. This effect was not due to a requirement of adenylate cyclase for Ca, since the cAMP level increase induced by forskolin was not Ca dependent. Furthermore isoproterenol induced 45Ca efflux, whereas forskolin did not. 45Ca efflux was correlated neither to cAMP nor to secretion, since when there was a massive augmentation of cAMP there was no change in 45Ca efflux, and forskolin, which induced much secretion, was unable to induce Ca efflux. Carbachol potentiated the secretion induced by forskolin in the absence of Ca, whereas it did not potentiate the isoproterenol-induced response. From these results we suggest that beta-adrenergic receptor activation would lead to two parallel events, cAMP accumulation and Ca movements, which together would lead to maximal secretion.

Microfilaments and cellular signal transduction: Effect of cytochalasin D on the production of cAMP, inositol phosphates, and on calcium movements in rat parotid glands

“…This pathway is mediated by the degradation of phosphatidylinositol bisphosphate and the concomitant production of inositol trisphosphate (IP3) and diacylglycerol (DG) and is associated with calcium fluxes [2,3,7,9,18,22,23,26,30]. By contrast protein secretion induced by the stimulation offl-adrenergic receptors is more efficient [14]. This pattern of secretion seems to be mediated by cyclic AMP accumulation [7,9,18,23].…”

“…This pattern of secretion seems to be mediated by cyclic AMP accumulation [7,9,18,23]. Moreover, we have recently reported [14] that fl-adrenergic receptor activation leads to two parallel events: cAMP accumulation and 45Ca efflux. These calcium movement.s are not a consequence of IP 3 production since we had shown that the IP 3 production was not affected by fladrenergic stimulation [15].…”

Process of re‐establishment of β‐adrenergic induced protein secretion after cytochalasin D inhibition in rat parotid gland. Effect of cholinergic agonist, phorbol ester and calcium

“…This pattern of secretion is mediated by cAMP accumulation [9,10,15]. Moreover, we had shown that in this tissue ~-adrenergic receptors activation lead to two parallel events: cAMP accumulation and 45Ca efflux [15]. These calcium movements are not a consequence of IP 3 production since we have shown that ~-adrenergic receptor activation is not able to induce any IP 3 production [15].…”

“…12-13 di-butyrate also on the cytoskeleton [7,12,13,15,17]. 12-13 di-butyrate also on the cytoskeleton [7,12,13,15,17].…”

A Ca2+-linked increase in coupled cAMP synthesis and hydrolysis is an early event in cholinergic and beta-adrenergic stimulation of parotid secretion.

“…Cholinergic stimuli effect this Ca2+ transient by a rapid generation of inositol 1,4,5-trisphosphate (InsP3) (23), 'whereas ,B-adrenergic agents do so by an undefined mechanism (24-26) that does not involve InsP3 (27) and that is independent of increases in cellular cAMP concentration (28). Also, since there are species of Ca2 +/calmodulinstimulable adenylyl cyclase (29) and phosphodiesterase (30) The mechanism that provides for such apparently fine coordination between cAMP synthesis and hydrolysis remains to be elucidated.…”