title: Opioid agonists inhibit excitatory neurotransmission in ganglia and at the neuromuscular junction in Guinea pig gallbladder.
abstract: OBJECTIVE
  Opiates administered therapeutically could have an inhibitory effect on the neuromuscular axis of the gallbladder, and thus contribute to biliary stasis and acalculous cholecystitis.
  
  
  METHODS
  Intracellular recordings were made from gallbladder neurons and smooth muscle, and tension measurements were made from muscle strips. Opioid receptor-specific agonists tested: delta, DPDPE; kappa, U-50488H; and mu, DAMGO.
  
  
  RESULTS
  Opioid agonists had no effect on gallbladder neurons or smooth muscle. Each of the opioid agonists potently suppressed the fast excitatory synaptic input to gallbladder neurons, in a concentration-dependent manner with half-maximal effective concentration values of about 1 pmol/L. Also, each agonist caused a concentration-dependent reduction in the amplitude of the neurogenic contractile response (half-maximal effective concentration values: DPDPE, 189 pmol/L; U-50488H, 472 pmol/L; and DAMGO, 112 pmol/L). These ganglionic and neuromuscular effects were attenuated by the highly selective opioid-receptor antagonist, naloxone. Opioid-receptor activation also inhibited the presynaptic facilitory effect of cholecystokinin in gallbladder ganglia. Immunohistochemistry with opioid receptor-specific antisera revealed immunostaining for all 3 receptor subtypes in nerve bundles and neuronal cell bodies within the gallbladder, whereas opiate-immunoreactive nerve fibers are sparse in the gallbladder.
  
  
  CONCLUSIONS
  These results show that opiates can cause presynaptic inhibition of excitatory neurotransmission at 2 sites within the wall of the gallbladder: vagal preganglionic terminals in ganglia and neuromuscular nerve terminals. These findings support the concept that opiates can contribute to gallbladder stasis by inhibiting ganglionic activity and neurogenic contractions.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Anatomy and Neurobiology, The University of Vermont College of Medicine, Burlington, Vermont 05405, USA.
authors.forename: Fay A
authors.initials: FA
authors.lastname: Guarraci
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Pozo
authors.forename: Sara M
authors.initials: SM
authors.lastname: Palomares
authors.forename: Tracy A
authors.initials: TA
authors.lastname: Firth
authors.forename: Gary M
authors.initials: GM
authors.lastname: Mawe
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001339:Autonomic Fibers, Preganglionic / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology; D002766:Cholecystokinin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D020881:Enkephalin, D-Penicillamine (2,5)- / Q000494:pharmacology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005260:Female; D005704:Gallbladder / Q000294:innervation*; D006168:Guinea Pigs; D007150:Immunohistochemistry; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009433:Neural Inhibition / Q000187:drug effects; D009469:Neuromuscular Junction / Q000737:chemistry / Q000502:physiology; D017465:Receptors, Opioid, delta / Q000032:analysis; D017473:Receptors, Opioid, kappa / Q000032:analysis; D017450:Receptors, Opioid, mu / Q000032:analysis; D009435:Synaptic Transmission / Q000187:drug effects*; D014630:Vagus Nerve / Q000166:cytology
chemical_list: D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D020881:Enkephalin, D-Penicillamine (2,5)-; D002766:Cholecystokinin