No Role for Phospholipase A₂ and Protein Kinase C in the Potentiation by α‐Adrenoceptors of β‐Adrenoceptor‐Mediated Cyclic AMP Formation in Rat Brain

Abstract

This study was undertaken to examine the role of phospholipase A2 and protein kinase C in the potentiation of beta-adrenoceptor-mediated cyclic AMP formation by alpha-adrenoceptors in rat cerebral cortical slices. Inhibition of arachidonic acid metabolism by a range of cyclooxygenase and lipoxygenase inhibitors had no effect on the potentiation of isoprenaline-stimulated cyclic AMP. Conversely, stimulation of leukotriene formation had no effect on the response to isoprenaline. The phospholipase A2 activator, melittin, stimulated cyclic AMP and potentiated the effect of isoprenaline, but these responses were not influenced by cyclooxygenase or lipoxygenase inhibitors. Indomethacin was also ineffective against the potentiation of vasoactive intestinal peptide-stimulated cyclic AMP by noradrenaline. Phorbol ester potentiated the cyclic AMP response to isoprenaline, and this potentiation was antagonized by three different putative protein kinase C inhibitors. However, the same inhibitors did not affect the alpha-adrenoceptor-stimulated enhancement of the response to isoprenaline. We have found no evidence, therefore, to support the suggestion that arachidonic acid and its metabolites and/or protein kinase C mediate the alpha-adrenoceptor modulation of beta-adrenoceptor function.

Protein Kinase C and Phospholipase C Mediate α‐ and β‐Adrenoceptor Intercommunication in Rat Hypothalamic Slices

“…To date it is unclear which is the mechanism by which al-recep-tors enhance cyclic AMP generation. Some studies have implicated PLC (Smith et al, 1979;Schimmel, 1988), PLA2 (Duman et al, 1986;Enna and Karbon, 1987;Schaad et al, 1987Schaad et al, , 1989Schimmel, 1988), or neither (Robinson and Kendall, 1989) in the mechanism of Equilibrated slices were incubated for 5 rnin with staurospodne or H7 or for 15 rnin with neomycin or quinacnne. All slices were then exposed to IS0 or vehicle for 20 min.…”

Mechanisms of Norepinephrine Mediated Corticotropin-Releasing Factor-41 Release from Cultured Fetal Hypothalamic Cells

“…Activation of catecholamine receptors leads to stimu lation of protein kinase C and protein kinase A pathways [14][15][16][17][18], and ai-adrenergic receptors have been shown to be coupled with phospholipase C, an enzyme which acti vates protein kinase C, in primary cultures of hypotha lamic neurons [ 13], Both protein kinase C and cAMP-de pendent protein kinase are involved as intracellular mess engers for CRF release [10,19,20]. These data clearly infer that NE-induced CRF release is likely to involve the activation of various G-proteins, protein kinase C or pro tein kinase A pathways.…”

“…Occupation of catecholamine receptors leads to the ac tivation of various G-proteins with consequent stimula tion of adenylate cyclase activity, induction of cellular cAMP formation and activation of PK-A, or increase phosphoinositide (PI) hydrolysis and activation of PK-C [13][14][15][16][17][18]. There is evidence that the release of CRF from cultured hypothalamic neurons can be activated by pro tein kinase C activators, phorbol esters and the protein kinase A stimulator, forskolin [10,19,20].…”

Cloning and expression of a Ca(2+)-inhibitable adenylyl cyclase from NCB-20 cells.

“…Indeed, a considerable number of reports indicate that neurotransmitters that increase [Ca2W]i also increase cAMP in brain slice preparations (5)(6)(7), although the precise mechanism has not been proven.…”