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Chronic reserpine (adrenergic blocking) treatment causes a marked accumulation of secretory protein in the rat submandibular gland (SMG) but discharge of this material is delayed in response to isoproterenol stimulation. The purposes of this study were to investigate the effects of chronic reserpine treatment on 1) the number of beta-adrenergic receptor. 2) the sensitivity of cell-surface-associated adenylate cyclase to various concentrations of isoproterenol, and 3) to correlate these data to morphologic studies of the secretion and resynthesis phases of the isoproterenol-induced secretory cycle in the rat SMG. Animals were injected with reserpine (0.5 microgram/g b.w.) for 6 days. Plasma membrane fractions were prepared. The adenylate cyclase response to a series of isoproterenol concentrations, and the number of beta-adrenergic receptors ([3H]-alprenolol binding) were determined. Other animals were given a single dose of isoproterenol (0.8 mg/100 g b.w.) and the SMG was examined by light and electron microscopy at various times (30 min to 24 h) after treatment. Chronic reserpine treatment leads to a 2.5-fold increase in SMG beta-adrenergic binding sites and a 50-fold increase in adenylate cyclase sensitivity to IPR stimulation when compared to controls. However, secretion and resynthesis of secretory product in response to IPR stimulation was greatly delayed in reserpinized rats.