Histamine H1 receptors mediate vasodilation in guinea-pig ileum resistance vessels: characterization with computer-assisted videomicroscopy and new selective agonists.
Histamine receptors on guinea-pig ileum submucosal arterioles (outside diameter 40-80 microns) were studied in vitro using a computer-assisted videomicroscopy system (Diamtrak). Histamine receptor agonists investigated in this study were histamine, the H1 receptor-selective compound, 2-[2-(3-fluorophenyl)-4-imidazolyl]ethanamine (VZ 20), the H2 receptor-selective compounds, dimaprit, impromidine, (+/-)-N1-[3-(4-fluorophenyl)-3-(pyridin-2-yl)propyl]- N2-[3-(1H-imidazol-4-yl)propyl]guanidine (arpromidine) and (+/-)-N1-[3-(3,4-difluorophenyl)-3-(pyridin-2-yl)propyl]- N2-[3-(1H-imidazol-4-yl)propyl]guanidine (BU-E-75), as well as the H3 receptor-selective drug, (R)-alpha-methylhistamine ((R)-alpha-MeHA). Applied to vessels at resting tone, the agonists (1 nM-300 microM) did not change arteriolar diameter. Vessels preconstricted by 10 microM noradrenaline showed similar concentration-dependent vasodilations with histamine and VZ 20 (pD2 = 5.38 and 5.36, respectively). This histamine-induced vasodilation was not affected by tetrodotoxin (0.5 microM) or indomethacin (1 microM), but was completely abolished in the presence of 1 microM of the H1 receptor antagonist, mepyramine. Calculation of the antagonist affinity of mepyramine for the histamine receptors in submucosal arterioles yielded a pA2 of 9.46. In contrast to histamine and VZ 20, the H2 receptor agonist, dimaprit, and the H3 receptor agonist, (R)-alpha-MeHA, were ineffective at preconstricted arterioles. The guanidine-type H2 receptor agonists, impromidine, apromidine and BU-E-75, produced vasodilation at noradrenaline-preconstricted arterioles (-log EC50 = 4.47, 5.30 and 5.39, respectively) but, in contrast to histamine, were ineffective at arterioles preconstricted by U-46619 (300 nM).(ABSTRACT TRUNCATED AT 250 WORDS)
Bungardt
E
E
Department of Pharmacology, University of Frankfurt, Germany.
Buschauer
A
A
Moser
U
U
Schunack
W
W
Lambrecht
G
G
Mutschler
E
E
D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D003201:Computers; D004305:Dose-Response Relationship, Drug; D006146:Guanidines / Q000494:pharmacology*; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology*; D007082:Ileum / Q000098:blood supply; D007093:Imidazoles / Q000494:pharmacology*; D017446:Impromidine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008853:Microscopy; D051381:Rats; D017208:Rats, Wistar; D011969:Receptors, Histamine H1 / Q000187:drug effects / Q000502:physiology*; D014649:Vas Deferens / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects*
D006146:Guanidines; D007093:Imidazoles; D011969:Receptors, Histamine H1; C069358:BU-E 75; D006632:Histamine; C060591:arpromidine; D017446:Impromidine