Veratridine-stimulated amylase secretion from rabbit pancreatic lobules: role of cholinergic and noncholinergic receptors.
Stimulation of pancreatic nerves results in marked increases in exocrine secretion. However, the neurotransmitters and pre- and postsynaptic receptors, which determine synaptic transmission between nerves and acinar cells, are poorly defined. We used rabbit pancreatic lobules, which contain nerve terminals and secrete independently of the influences of vascular perfusion or gastrointestinal hormones, to study the role of cholinergic and noncholinergic nerves in regulating amylase secretion. Pancreatic nerves were stimulated by veratridine (Ver; 50-200 microM), an activator of voltage-dependent sodium channels, in a concentration-dependent and tetrodotoxin-sensitive manner, resulting in an increase of 138+/-15% in amylase secretion above basal at 100 microM. This stimulation was unaffected by either hexamethonium (100 microM) or the combination of phentolamine and propranolol (10 microM). Atropine (5 microM) inhibited Ver-stimulated secretion by approximately 65-70%. Bethanechol (Bch; 0.01-100 microM) increased amylase secretion in a concentration-dependent manner (EC50, 6.2 microM), with a maximal stimulation of 177+/-15% above basal. Antagonism of Bch-stimulated secretion with 4-diphenylacetoxy-N-methyl-piperidine, pirenzepine (Pzp), or methoctramine (Met) resulted in IC50 values of 7.9 nM, 282 nM, and 79.8 microM, respectively. Ver-stimulated secretion was unaffected by Pzp (0.1 and 1 nM) or Met (1 and 100 nM) at concentrations that had no significant effect on Bch-stimulated secretion. Thus cholinergic nerves, activating postsynaptic M3 receptors, provided the predominant stimulatory innervation of rabbit pancreatic acini. Nonadrenergic, noncholinergic nerves also made a significant contribution to secretion. Adrenergic nerves did not appear to innervate acini or the excitatory cholinergic nerves directly.
Love
J A
JA
Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson 39216-4505, USA.
Szebeni
K
K
Smith
T G
TG
D018674:Adrenergic Antagonists / Q000494:pharmacology; D000681:Amylases / Q000378:metabolism*; D000818:Animals; D018723:Bethanechol / Q000494:pharmacology; D018680:Cholinergic Antagonists / Q000494:pharmacology; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009412:Nerve Fibers / Q000187:drug effects; D010179:Pancreas / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D011817:Rabbits; D011950:Receptors, Cholinergic / Q000502:physiology; D011976:Receptors, Muscarinic / Q000502:physiology; D017981:Receptors, Neurotransmitter / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D013268:Stimulation, Chemical; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors; D014701:Veratridine / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D018674:Adrenergic Antagonists; D018680:Cholinergic Antagonists; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D011950:Receptors, Cholinergic; D011976:Receptors, Muscarinic; D017981:Receptors, Neurotransmitter; D018723:Bethanechol; D013779:Tetrodotoxin; D014701:Veratridine; D000681:Amylases