Role of adrenergic receptors in veratridine-stimulated amylase secretion from rabbit pancreatic lobules

Sympathetic inhibition of pancreatic enzyme secretion has been attributed t o vasoconstriction and direct inhibition of acinar cells. We observed both adrenergic inhibition and facilitation of cholinergic transmission in rabbi t pancreatic ganglia, which innervate acini. Here we used pancreatic lobule s to determine whether adrenergic receptors also regulate synaptic transmis sion between pancreatic nerves and acini. Stimulation of pancreatic nerve t erminals with veratridine (Ver), an activator of voltage-dependent Na+ chan nels, resulted in a 102% increase in amylase secretion, which was unaffecte d by alpha and beta receptor antagonists but inhibited 65% by atropine. At a concentration of 10 mu M, norepinephrine inhibited (38%) and epinephrine potentiated (40%) Ver-stimulated secretion. At the same concentration, the alpha(2) agonist clonidine (Clon) inhibited (39%), whereas the nonselective beta agonist isoproterenol (Iso) and the selective beta(3) agonist BRL 373 44 potentiated (71 and 67%, respectively) nerve-stimulated secretion. The e ffects of Cion and Iso and BRL 37344 were antagonized by yohimbine and prop ranolol, respectively. Phenylephrine, dobutamine, and terbutaline had no ef fect. Neither basal, bethanechol-stimulated, nor noncholinergic nerve-stimu lated secretion was significantly altered by Cion or Iso. Thus, cholinergic nerve terminals innervating pancreatic acini exhibit both inhibitory alpha (2) and atypical facilitatory beta adrenergic receptors. The apparent lack of adrenergic innervation suggests that adrenergic receptors on the nerve t erminals of cholinergic pancreatic neurons are under hormonal control by ci rculating catecholamines. These results provide further evidence that intri nsic pancreatic neurons, which supply most, if not all, of the cholinergic innervation of acini, are important sites of sympathetic regulation of panc reatic exocrine secretion.