Analysis of protein synthesis in rat salivary glands after chronic treatment with beta-receptor agonists and phosphodiesterase inhibitors.
Chronic administration of the beta-adrenergic receptor agonist isoproterenol (5 mg/200 g animal for 10 days) resulted in rat parotid and submandibular gland hypertrophy, and it induced synthesis of a series of proline-rich proteins (PRPs) and glycoproteins. Treated parotid glands additionally exhibit an increase in activity for the Golgi membrane enzyme UDP-galactose; N-acetylglucosamine 4 beta-galactosyltransferase. A series of beta-receptor agonists and phosphodiesterase inhibitors were examined for their abilities to influence salivary gland protein biosynthesis in a fashion similar to that observed with chronic isoproterenol treatment. beta 1/beta 2-Adrenergic-receptor agonists exhibited the greatest effects on parotid gland hypertrophy and PRP biosynthesis. These beta-agonists were also able to increase 4 beta-galactosyltransferase activity, but they did not promote the synthesis of a 220,000 dalton glycoprotein. Terbutaline (beta 2-receptor agonist) induced parotid gland hypertrophy but was only able to induce protein biosynthesis at higher drug concentrations. Finally, methoxyphenamine was unable to produce the observed changes in protein synthesis even at increased drug dosages. The phosphodiesterase inhibitors (theophylline and caffeine) were able to induce de novo PRP biosynthesis at drug doses of 20 mg/200 g animal. However, while causing mild gland hypertrophy, there was no observable change in 4 beta-galactosyltransferase activity with either phosphodiesterase inhibitor. This same regimen of beta-receptor agonists was unable to induce submandibular gland hypertrophy, PRP or glycoprotein biosynthesis in the same animals. This was also true for the two phosphodiesterase inhibitors. Co-injection of a beta 1 antagonist along with isoproterenol blocked the above protein changes in both the submandibular and parotid glands, suggesting that the stimulation of protein synthesis takes place by beta 1-type receptors on the gland cell surfaces.
Wells
D J
DJ
Humphreys-Beher
M G
MG
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D000242:Cyclic AMP / Q000032:analysis; D005700:Galactosyltransferases / Q000032:analysis; D006023:Glycoproteins / Q000096:biosynthesis; D006984:Hypertrophy; D008297:Male; D010452:Peptide Biosynthesis; D010455:Peptides; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D055232:Proline-Rich Protein Domains; D014176:Protein Biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D012469:Salivary Glands / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology
D000318:Adrenergic beta-Agonists; D006023:Glycoproteins; D010455:Peptides; D010726:Phosphodiesterase Inhibitors; D011943:Receptors, Adrenergic, beta; D000242:Cyclic AMP; D005700:Galactosyltransferases