Propranolol inhibits cyclic AMP accumulation and amylase secretion in parotid acinar cells stimulated by isobutylmethylxanthine and forskolin.
Propranolol inhibited cyclic AMP (cAMP) accumulation stimulated by 3-isobutyl-1-methylxanthine (IBMX) or forskolin in rat parotid acinar cells. The inhibition by propranolol was highly potent; 10(-7) M propranolol was sufficient for the maximum inhibition (approx. 50% at 5 min). The inhibitory effect was observed in both intact and saponin-permeabilized parotid cells, but the effect was more prominent in permeabilized cells than in intact cells. Other beta-blockers, like alprenolol and atenolol, were as effective as propranolol, but butoxamine (beta 2-selective) was slightly less effective. The inhibition by propranolol was similarly detected in the cells prepared from pertussis-toxin-pretreated rats, suggesting that inhibitory guanine nucleotide regulatory protein (Gi) is not involved in the inhibitory mechanism. Propranolol also inhibited the exocytosis of amylase stimulated by IBMX or forskolin. In the presence of propranolol and IBMX, the responsiveness of saponin-permeabilized cells to exogenous cAMP was markedly increased, indicating that propranolol neither promotes the degradation of cAMP nor prevents the inhibitory effect of IBMX on cAMP phosphodiesterase.
Takuma
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Department of Oral Biochemistry, School of Dentistry, Higashi Nippon Gakuen University, Hokkaido, Japan.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology*; D000526:Alprenolol / Q000494:pharmacology; D000681:Amylases / Q000378:metabolism*; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D002078:Butoxamine / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D010306:Parotid Gland / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012503:Saponins / Q000494:pharmacology; D013806:Theophylline / Q000031:analogs & derivatives*
D008565:Membrane Proteins; D012503:Saponins; D002078:Butoxamine; D005576:Colforsin; D001262:Atenolol; D000526:Alprenolol; D011433:Propranolol; D013806:Theophylline; D000242:Cyclic AMP; D011065:Poly(ADP-ribose) Polymerases; D000681:Amylases; D015056:1-Methyl-3-isobutylxanthine