Bromoacetylalprenololmenthane: a potent irreversible antagonist of beta adrenergic elicited protein exocytosis in rat parotid cells.
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.
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
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