Pharmacological characterization of histamine H-3 receptors in human saphenous vein and guinea pig ileum

Studies were performed to assess the functional activity of histamine H-3 r eceptors on neurogenic sympathetic end organ responses in cryopreserved hum an saphenous vein. (R)-alpha-methylhistamine inhibited electrical field sti mulation-evoked contractile responses in a dose dependent manner (pD(2) = 8 .20). Prazosin (1 mu M) and tetrodotoxin (1 mu M) blocked the electrical fi eld stimulation-evoked contractile responses in human saphenous vein indica ting a sympathetic neural origin of these contractions. The histamine H-3 a ntagonists thioperamide (pA(2) = 8.41) and clobenpropit (pA(2) = 10.10) pro duced parallel rightward shifts in the concentration response curve to (R)- alpha-methylhistamine in human saphenous vein and guinea pig ileum (pA(2) = 8.59 and 9.83, respectively). Pretreatment with (R)-alpha-methylhistamine (1 mu M) did not alter contractions to exogenous norepinephrine in human sa phenous vein. In addition, clonidine (pD(2) = 10.28) inhibited electrical f ield stimulation-evoked contractile responses in human saphenous vein which were blocked by yohimbine (30 nM, pA(2) = 9.92) but did not alter the (R)- alpha-methylhistamine dose response curve. These results demonstrate the pr esence of functional presynaptic histamine H-3 heteroreceptors on cryoprese rved human saphenous vein sympathetic nerves that, upon activation, attenua te electrical held stimulation-evoked contractile responses in this vessel. (C) 1999 Elsevier Science B.V. All rights reserved.