title: Role of adrenergic receptors in veratridine-stimulated amylase secretion from rabbit pancreatic lobules.
abstract: Sympathetic inhibition of pancreatic enzyme secretion has been attributed to vasoconstriction and direct inhibition of acinar cells. We observed both adrenergic inhibition and facilitation of cholinergic transmission in rabbit pancreatic ganglia, which innervate acini. Here we used pancreatic lobules to determine whether adrenergic receptors also regulate synaptic transmission between pancreatic nerves and acini. Stimulation of pancreatic nerve terminals with veratridine (Ver), an activator of voltage-dependent Na+ channels, resulted in a 102% increase in amylase secretion, which was unaffected by alpha and beta receptor antagonists but inhibited 65% by atropine. At a concentration of 10 microM, norepinephrine inhibited (38%) and epinephrine potentiated (40%) Ver-stimulated secretion. At the same concentration, the alpha2 agonist clonidine (Clon) inhibited (39%), whereas the nonselective beta agonist isoproterenol (Iso) and the selective beta3 agonist BRL 37344 potentiated (71 and 67%, respectively) nerve-stimulated secretion. The effects of Clon and Iso and BRL 37344 were antagonized by yohimbine and propranolol, respectively. Phenylephrine, dobutamine, and terbutaline had no effect. Neither basal, bethanechol-stimulated, nor noncholinergic nerve-stimulated secretion was significantly altered by Clon or Iso. Thus, cholinergic nerve terminals innervating pancreatic acini exhibit both inhibitory alpha2 and atypical facilitatory beta adrenergic receptors. The apparent lack of adrenergic innervation suggests that adrenergic receptors on the nerve terminals of cholinergic pancreatic neurons are under hormonal control by circulating catecholamines. These results provide further evidence that intrinsic pancreatic neurons, which supply most, if not all, of the cholinergic innervation of acini, are important sites of sympathetic regulation of pancreatic exocrine secretion.
authors.affiliation: Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson 39216-4505, USA. jlove@pharmacology.umsmed.edu
authors.forename: J A
authors.initials: JA
authors.lastname: Love
authors.forename: K
authors.initials: K
authors.lastname: Szebeni
authors.forename: T G
authors.initials: TG
authors.lastname: Smith
mesh_terms: D000322:Adrenergic Agonists / Q000494:pharmacology; D018674:Adrenergic Antagonists / Q000494:pharmacology; D000681:Amylases / Q000378:metabolism*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D010646:Phentolamine / Q000494:pharmacology; D011817:Rabbits; D011941:Receptors, Adrenergic / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects; D014701:Veratridine / Q000494:pharmacology*
chemical_list: D000322:Adrenergic Agonists; D018674:Adrenergic Antagonists; D018721:Muscarinic Agonists; D011941:Receptors, Adrenergic; D014701:Veratridine; D001285:Atropine; D000681:Amylases; D009638:Norepinephrine; D004837:Epinephrine; D010646:Phentolamine