Histamine receptor type coupled to nitric oxide-induced relaxation of guinea-pig nasal mucosa.
1 The aim of this study was to characterize the histamine receptor type mediating relaxation of the vascular bed of the nasal mucosa from the guinea-pig, and to determine the role of cyclo-oxygenase products and nitric oxide in this relaxant response to histamine. These studies were performed in isolated nasal mucosae examined in vitro to obtain potencies of histamine receptor-type selective agonists in causing vasorelaxation and to determine affinities of histamine receptor antagonists for inhibiting histamine-induced relaxation. 2 After contraction of nasal mucosae with noradrenaline, histamine caused a maximal relaxation response that was 75 +/- 6% of the contraction caused by noradrenaline with a mean EC50 value of 4.3 +/- 0.5 microM. Neither dimaprit (H2-receptor selective) nor R-alpha-methylhistamine (H3-receptor selective) caused significant relaxation of nasal mucosae. In contrast, betahistine (H1-receptor selective) caused an 81 +/- 7% relaxation of noradrenaline-induced tone with an EC50 value of 15 +/- 1 microM. 3 pA2 experiments were performed to obtain KB values of chlorpheniramine (H1-receptor selective) and diphenhydramine (H1-receptor selective) for blocking histamine-stimulated relaxation of nasal mucosae. KB values for chlorpheniramine (0.87 nM) and diphenhydramine (7.4 nM) were consistent with their interaction at the H1-receptor type. Additionally, neither 10 microM cimetidine (H2-receptor selective) nor 1 microM thioperamide (H3-receptor selective) had any effect on the relaxation curve for histamine. 4 In the presence of 10 microM indomethacin (cyclo-oxygenase inhibitor), histamine caused a maximal relaxation response of 73 +/- 5% of the noradrenaline-induced tone with an EC50 value of 2.9 +/- 0.2 microM, which was not different from control values (EC50 = 5.0 +/- 0.4 microM; maximal relaxation = 71 +/- 6%). In contrast, 200 microM NG-nitro-L-arginine (nitric oxide synthase inhibitor) completely inhibited histamine-induced relaxation of nasal mucosae. 5 In conclusion, data from the present study suggest only the H1-receptor type mediates relaxation of nasal mucosal blood vessels to histamine, and histamine-induced relaxation of nasal mucosae is entirely dependent on nitric oxide production.
Bockman
C S
CS
Department of Pharmacology, Creighton University School of Medicine, 2500 California Plaza, Criss III, Room 553, Omaha, NE 68178, USA.
Zeng
W
W
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D006633:Histamine Antagonists / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009297:Nasal Mucosa / Q000187:drug effects*; D009569:Nitric Oxide / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011968:Receptors, Histamine / Q000187:drug effects*; D018100:Receptors, Histamine H3 / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D006633:Histamine Antagonists; D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D011968:Receptors, Histamine; D018100:Receptors, Histamine H3; D019335:Nitroarginine; D009569:Nitric Oxide; D006632:Histamine; D019001:Nitric Oxide Synthase; D011451:Prostaglandin-Endoperoxide Synthases; D009638:Norepinephrine; D007213:Indomethacin