Beta‐adrenergic receptor mechanisms in rat parotid glands: activation by nerve stimulation and 3‐isobutyl‐1‐methylxanthine.

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Abstract
The technique of electrical field stimulation (e.f.s.) was employed in conjunction with selective pharmacological antagonists to specifically investigate the role of endogenous neurotransmitter(s) in the activation of .beta.-adrenergic receptor mechanisms in isolated parotid gland segments of the rat. The field-stimulus-induced amylase release due to .beta.-adrenergic receptor activation was characterized as that persisting in the presence of atropine (10-5 M) and phentolamine (10-5 M) and susceptible to blockade by propranolol (5 .times. 10-6 M), i.e., combined .beta.1- and .beta.2-receptor blockade. The selective .beta.1-receptor antagonist metoprolol (10-5 M) was as effective as propranolol in blocking the .beta.-mediated enzyme release. The selective .beta.2-receptor antagonist, H35/25 [.alpha.,4-dimethyl-N-isopropylphenylethanolamine] (10-5 M) did not significantly affect the field stimulus-induced amylase release. In the absence of any phosphodiesterase inhibitor the levels of cAMP in the tissues were close to the limit of detection. Field stimulation was associated with a 4-fold increase in cAMP. By comparison isoprenaline (10-5 M) gave rise to 10-fold increase in cAMP. The changes in cAMP metabolism, in response to both field stimulation and isoprenaline, were greatly enchanced in the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX). The field stimulus-induced increase in cAMP was abolished by the .beta.1-adrenergic receptor antagonist, metoprolol, but persisted in the presence of the .beta.2-adrenergic antagonist, H35/25. IBMX had a potent direct effect on amylase release. IBMX (10-3 M) also gave rise to a 10-fold increase in cAMP. IBMX is then as effective as 10-5 M isoprenaline in stimulating both enzyme secretion and cAMP metabolism. The secretory response to IBMX was unaffected by .beta.-adrenergic blockade by propranolol, was independent of extracellular Ca and did not give rise to 86Rb+ efflux. Importantly, isoprenaline (10-5 M) failed to evoke any significant increase in amylase release if introduced during sustained superfusion of IBMX, yet it is in such protocols that the greatest changes in cAMP metabolism are seen. The .beta.-adrenergic-receptor-regulated amylase release in response to nerve stimulation is mediated predominantly, if not exclusively, by the .beta.1-receptor subtype. The changes in cAMP measured in the presence of the phosphodiesterase inhibitor, IBMX, do not correlate with enzyme secretion.