Characterization of pre- and postsynaptic muscarinic receptors in circular muscle of pig gastric fundus.
1. This study investigated the subtype of muscarinic receptors on the cholinergic neurones and smooth muscle in the circular muscle of the pig gastric fundus. 2. Muscarinic antagonists, except MT-3, concentration-dependently inhibited the contractions induced by a given concentration of acetylcholine. Concentration-response curves by acetylcholine were shifted rightwards in a parallel manner without depression of the maximum by the muscarinic antagonists, except by MT-3 that induced a leftward shift. Correlation of the pIC(50) and pA(2) values with published pK(i) values for the five muscarinic receptor subtypes suggests that the muscarinic receptors on pig gastric fundus circular muscle belong to the M(3) subtype. 3. Electrically-evoked contractions (40 V, 4 Hz, 0.25 ms, 2 min) were concentration-dependently inhibited by the muscarinic antagonists except for methoctramine and AF-DX 116, that increased the amplitude of the electrically-induced contractions in lower concentrations. MT-3 tended to increase the electrically-induced contractions. 4. The antagonists, except MT-3, concentration-dependently increased the electrically-induced tritium outflow (40 V, 4 Hz, 0.25 ms, 2 min) after incubation of the tissues with [(3)H]-choline. MT-3 (3 x 10(-8) and 10(-7) M) decreased the electrically-induced tritium release. Correlation of the pIC(50) values with published pK(i) values for the different muscarinic receptor subtypes yielded a significant and comparable correlation for M(1), M(3), M(4) and M(5) receptors. 5. These results suggest that the postsynaptic receptors in circular muscle of the pig gastric fundus belong to the M(3) subtype. However, the presynaptic receptor could not be clearly defined, although it does certainly not belong to the M(2) subtype.
Leclere
Pascal G
PG
Heymans Institute of Pharmacology, Ghent University, Faculty of Medicine and Health Sciences, De Pintelaan 185, B-9000 Ghent, Belgium.
Lefebvre
Romain A
RA
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D004558:Electric Stimulation; D005748:Gastric Fundus / Q000502:physiology*; D066298:In Vitro Techniques; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D043587:Receptor, Muscarinic M3; D011976:Receptors, Muscarinic / Q000145:classification* / Q000502:physiology*; D013552:Swine; D009435:Synaptic Transmission
D018727:Muscarinic Antagonists; D043587:Receptor, Muscarinic M3; D011976:Receptors, Muscarinic; D000109:Acetylcholine