Role of L- and N-type Ca2+ channels in muscarinic receptor-mediated facilitation of ACh and noradrenaline release in the rat urinary bladder

J Physiol. 1997 Mar 15;499 ( Pt 3)(Pt 3):645-54. doi: 10.1113/jphysiol.1997.sp021957.

Abstract

1. 3H-Noradrenaline (NA) and 14C-acetylcholine (ACh) released by electrical field stimulation were measured simultaneously in strips from the body of rat urinary bladder. 2. omega-Conotoxin GVIA (omega-CgTX; 20-100 nM) suppressed the non-facilitated transmitter release evoked by intermittent stimulation (IS), whereas nifedipine (1 microM) did not affect release. 3. Continuous electrical stimulation (CS) facilitated NA and ACh release via an atropine-sensitive mechanism. omega-CgTX reduced the facilitated release of NA (44% depression) but did not affect ACh release. Nifedipine depressed ACh release (43%) but not NA release. Combined administration of nifedipine and omega-CgTX (20 nM) produced a greater suppression of NA and ACh release (86 and 91%, respectively). 4. Maximal muscarinic facilitation of NA (5-fold) and ACh (17-fold) release occurred following administration of eserine, an anticholinesterase agent. Release of both NA and ACh was depressed by nifedipine (70 and 83%, respectively) but not by omega-CgTX. Combined application of omega-CgTX and nifedipine elicited a further depression of NA (95%) but not ACh release. 5. When NA and ACh release was facilitated with phorbol dibutyrate (0.5 microM), nifedipine inhibited ACh (67%) but not NA release, whereas omega-CgTX inhibited NA (73%) but not ACh release. Combined administration of both Ca2+ channel blockers did not elicit greater inhibition. 6. Bay K 8644, the L-type Ca2+ channel activator, increased ACh release in a dose-dependent manner (up to 5-fold) but did not significantly change NA release. 7. Both omega-CgTX (20-100 nM) and nifedipine (100 nM-1 microM) significantly decreased (50-80%) the neurally evoked contractions of the bladder strips. 8. It is concluded that L-type Ca2+ channels play a major role in muscarinic facilitation of NA and ACh release in the urinary bladder but are not essential for non-facilitated release. Other types of Ca2+ channels, including N-type, are involved to varying degrees in non-facilitated and facilitated release under different experimental conditions.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / pharmacology
  • Acetylcholine / metabolism*
  • Animals
  • Calcium Channel Agonists / pharmacology
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels / drug effects
  • Calcium Channels / metabolism*
  • Calcium Channels, L-Type
  • Electric Stimulation
  • Evoked Potentials / drug effects
  • Male
  • Nifedipine / pharmacology
  • Norepinephrine / metabolism*
  • Peptides / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Muscarinic / drug effects
  • Receptors, Muscarinic / metabolism*
  • Urinary Bladder / metabolism*
  • omega-Conotoxin GVIA

Substances

  • Calcium Channel Agonists
  • Calcium Channel Blockers
  • Calcium Channels
  • Calcium Channels, L-Type
  • Peptides
  • Receptors, Muscarinic
  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
  • omega-Conotoxin GVIA
  • Nifedipine
  • Acetylcholine
  • Norepinephrine