title: Bromoacetylalprenololmenthane: a potent irreversible antagonist of beta adrenergic elicited protein exocytosis in rat parotid cells.
abstract: The interaction of bromoacetylalprenololmenthane (BrAlpM), an irreversible beta adrenergic receptor antagonist, with rat parotid acinar cells was studied in vitro. In the presence of BrAlpM, the rate of (-)-isoproterenol-induced exocrine secretion from cells, measured as percentage of amylase release, was markedly reduced. The concentration of (-)-isoproterenol required to elicit half-maximal protein secretion was about 100 times greater (5 microM) in the presence of 1 microM BrAlpM than in control incubations (0.05 microM). BrAlpM and propranolol were similar in their ability to inhibit parotid protein release (IC50 approximately 10(-7) M). To demonstrate that BrAlpM functioned as an irreversible beta adrenergic antagonist, cells were preincubated with BrAlpM for varying amounts of time and then washed three to six times before adding (-)-isoproterenol. At least 10 min preincubation was required to show irreversibility. Alprenolol, under the same preincubation conditions, was unable to inhibit amylase release. BrAlpM inhibited the binding of [3H]dihydroalprenolol to parotid beta adrenoreceptors over a concentration range similar to that required for inhibition of protein secretion. Cells incubated in the absence or presence of BrAlpM displayed a comparable morphologic appearance when viewed by light and electron microscopy. The degree of inhibition of isoproterenol-induced exocytosis of secretory granules by BrAlpM appeared to vary from cell to cell. These findings suggest that BrAlpM should be a useful probe to study beta adrenoreceptor function and metabolism in rat parotid acinar cells.
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000526:Alprenolol / Q000031:analogs & derivatives* / Q000494:pharmacology; D000681:Amylases / Q000378:metabolism; D000818:Animals; D000081005:Cyclohexane Monoterpenes; D003864:Depression, Chemical; D004082:Dihydroalprenolol / Q000378:metabolism; D005089:Exocytosis / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008854:Microscopy, Electron; D010306:Parotid Gland / Q000187:drug effects* / Q000648:ultrastructure; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology
chemical_list: D000319:Adrenergic beta-Antagonists; D000081005:Cyclohexane Monoterpenes; D011943:Receptors, Adrenergic, beta; D004082:Dihydroalprenolol; C028417:1-(2-allylphenoxy)-3-((8-bromoacetylamino-4-menthane-1-yl)amino)-1-propanol; C028416:1-(2-allylphenoxy)-3-((1-bromoacetylamino-4-menthane-8-yl)amino)-2-propanol; D000526:Alprenolol; D000681:Amylases; D007545:Isoproterenol