Quantitative structural analysis and the secretory behaviour of the rat parotid gland after long and short term isoprenaline treatment.

Isoprenaline (IPR) was administered as daily subcutaneous injections into newborn rats for a period of 9 weeks (long-term treatment) and into 8 week-old rats for 10 days (short-term treatment). Both the parotid and the submandibular glands increased five- to six-fold in weight in the two groups due to hypoertrophy as well as to hyperplasia. The parotid glands were subjected to electron microscopic stereological analyses and to in vitro secretory studies. The results were compared with non-treated controls. Whereas mean total cell volume in the latter was 807 microns 3 it amounted to 5804 microns 3 in glands from long-term IPR-treated rats. A striking increase in size and number of cytoplasmic granules was noted after IPR treatment; there was also a marked decrease in granule electron density as compared with control cells. Granule volume density was 31.2 +/- 1.8% in controls and 58.0 +/- 1.5% in long-term IPR-treated rats. The increase in volume density, however, was accompanied by a relative decrease in amylase and cyclic AMP contents. On a percentage basis, the basal secretion of amylase from incubated IPR-treated parotid glands was markedly higher (roughly twice) than that of control glands; the absolute release of amylase into the medium, however, was only slightly increased. Basal secretion was not energy requiring, which would suggest a passive diffusion. Stimulation by beta-adrenoceptor agonists, including beta 1 and beta 2 selective agents, had no or only a small stimulatory effect in vitro on IPR-treated glands. Dibutyryl cyclic AMP was effective in controls but not in treated glands. Cholinergic stimulation caused a considerable amylase release from glands of IPR-treated rats; this release was comparable to that obtained in controls. The results suggest that superstimulation of the beta-adrenoceptor leads to a decreased sensitivity for adrenergic agonists. This may be due to membrane changes (e.g. modified receptor sites) and/or to an altered intracellular metabolism (e.g. a modified turnover of cyclic nucleotides).