Muscarinic receptors involved in modulation of norepinephrine release and vasodilatation in guinea pig carotid arteries.
Acetylcholine (ACh, 1-50 microM) and carbachol (1-10 microM) concentration-dependently enhanced the electrically evoked tritium overflow in guinea pig carotid arteries preincubated with [3H]norepinephrine (NE). However, lower concentrations of ACh and carbachol (0.05 and 0.1 microM) slightly reduced this overflow. Phentolamine (1 microM) potentiated the inhibitory and reduced the facilitatory effects of ACh, whereas hexamethonium (300 microM) did not modify either effect. Several muscarinic receptor antagonists shifted both ACh effects to the right. The order of potencies (apparent pKb values) was, for the facilitatory effect, atropine (10.14) > pirenzepine (8.66) > p-fluoro-hexahydrosila-difenidol (p-F-HHSiD) (6.82) > or = to methoctramine (6.33), and the order for the inhibitory effect in the presence of phenotolamine was atropine (10.00) > methoctramine (7.86) > or = to AF-DX 116 (7.70) > pirenzepine (6.72) > p-F-HHSiD (6.00). ACh (0.01-10 microM) induced endothelium-dependent vasodilatation in perfused segments of guinea pig carotid arteries, and this effect was competitively inhibited by the above-mentioned muscarinic receptor antagonists. The order of potencies (pA2 values) was atropine (9.96) > p-F-HHSiD (8.05) > pirenzepine (7.64) > methoctramine (6.83). These results suggest that the noradrenergic nerve endings in guinea pig carotid arteries possess M2 inhibitory and M1 facilitatory muscarinic receptors that modulate NE release, and the endothelial cells possess M3 muscarinic receptors that mediate ACh-induced vasodilatation.
Casado
M A
MA
Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma, Madrid, Spain.
Sevilla
M A
MA
Alonso
M J
MJ
Marin
J
J
Salaices
M
M
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002339:Carotid Arteries / Q000502:physiology; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000145:classification / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects*
D011976:Receptors, Muscarinic; D001285:Atropine; D000109:Acetylcholine; D009638:Norepinephrine