Spasmolytic effects of three harmala alkaloids on guinea-pig isolated trachea.
The present study examined and compared the spasmolytic effects of 3 harmala alkaloids, harmine, harman, and harmaline, on carbachol-, histamine-, and KCl-induced contractions of guinea-pig isolated tracheal preparations. All 3 compounds relaxed the tracheal preparations contracted by these spasmogens with similar or different EC50 values, harmine being the most potent one. The cumulative concentration-response curves of all 3 compounds for carbachol-induced contraction were shifted to the right by propranolol (1 microM) pretreatment, indicating the involvement of the activation on the beta-adrenoceptors. All 3 compounds shifted the concentration-response curves of carbachol to the right in a parallel manner with the pA2 values comparable with their relaxation EC50 values, indicating a competitive antagonism at the muscarinic receptors. Receptor binding assays indicated that all 3 compounds interacted with lung muscarinic receptors (Ki = 11-13 microM), histamine H1 receptors (Ki = 27-107 microM), and beta2-adrenoceptors (Ki = 20-51 microM). Therefore, in addition to their actions on receptor-linked and voltage-dependent Ca2+ channels as reported in other types of smooth muscle, the present study suggests that the actions on muscarinic receptors, histamine H1 receptors, and beta2-adrenoceptors are also involved in their spasmolytic effects on airway smooth muscles.
Shi
C C
CC
Department and Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan.
Liao
J F
JF
Chen
C F
CF
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D015220:Calcium Channels / Q000187:drug effects; D002217:Carbachol / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006246:Harmaline / Q000031:analogs & derivatives / Q000494:pharmacology; D006247:Harmine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology; D006633:Histamine Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D010276:Parasympatholytics / Q000494:pharmacology*; D011189:Potassium Chloride / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects / Q000378:metabolism; D011969:Receptors, Histamine H1 / Q000187:drug effects / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism; D014132:Trachea / Q000187:drug effects* / Q000502:physiology
D000319:Adrenergic beta-Antagonists; D000470:Alkaloids; D015220:Calcium Channels; D006633:Histamine Antagonists; D018727:Muscarinic Antagonists; D010276:Parasympatholytics; D018343:Receptors, Adrenergic, beta-2; D011969:Receptors, Histamine H1; D011976:Receptors, Muscarinic; D006247:Harmine; D011189:Potassium Chloride; D006632:Histamine; C005010:harman; D002217:Carbachol; D011433:Propranolol; D006246:Harmaline