Short-term exposure to somatostatin or muscarinic agonists reduce acetylcholine-induced 3H-MPP+ release from bovine adrenal medullary cells.
The aim of this work was to investigate the effect of a short-term exposure to somatostatin (SS), its receptors (SSTR) selective agonists as well as muscarinic receptors agonists upon acetylcholine-induced release of (3)H-MPP(+ )from bovine adrenal medullary cells. Acetylcholine (ACH, 100, 500 microM) was found to increase the release of (3)H-MPP(+ )by these cells (to 175 and 171% of basal release, respectively). ACH-elicited (3)H-MPP(+) release was significantly reduced by hexamethonium (100 microM) and atropine (100 microM), selective nicotinic and muscarinic antagonists, respectively. Previous exposure to any of two muscarinic agonists, oxotremorine or pilocarpine, led to a significant reduction of (3)H-MPP(+) release in response to 100 microM ACH, to about a maximum of 51% and 78% of control, respectively. Somatostatin (SS, 0.01-0.1 microM), previously applied to the preparation, depressed ACH-elicited (3)H-MPP(+ )release by 25-27%, but only when a 500 microM ACH concentration was used. The inhibition exerted by SS upon ACH-evoked (3)H-MPP(+) release appeared to be mediated by its SSTR: (1) SSTR2, 3 and 4 subtype agonists mimicked the effects seen with SS, and (2) the SSTR non-selective antagonist, cyclo-SS, counteracted the SS inhibitory effect. When SS was tested in the presence of any of the muscarinic agonists, oxotremorine or pilocarpine, its inhibitory effect on 500 microM ACH-induced (3)H-MPP(+) release was no longer detectable. These results, showing a somewhat similar effect of short-term exposure to SS and muscarinic agonists over ACH-induced release of (3)H-MPP(+), as well as the loss of effect of SS by the presence of the muscarinic agonists, suggest that these compounds may share signalling pathways.
Ribeiro
Laura
L
Department of Biochemistry (U38-FCT), Faculty of Medicine, University of Porto, 4200-319, Porto, Portugal. lribeiro@med.up.pt
Martel
Fãtima
F
Azevedo
Isabel
I
D015655:1-Methyl-4-phenylpyridinium / Q000378:metabolism*; D000109:Acetylcholine / Q000378:metabolism*; D000313:Adrenal Medulla / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D004347:Drug Interactions; D018721:Muscarinic Agonists / Q000494:pharmacology*; D013004:Somatostatin / Q000494:pharmacology*
D018721:Muscarinic Agonists; D013004:Somatostatin; D000109:Acetylcholine; D015655:1-Methyl-4-phenylpyridinium