组胺受体在致敏豚鼠心室肌延迟后除极和触发活动中的作用

采用微电极细胞内记录和电子计算机实时采样技术,研究了组胺受体在特异性抗原（卵清白蛋白,０．２５μｍｏｌ／Ｌ）对致敏豚鼠心室乳头肌动作电位的影响中的作用。心性过敏反应可诱发延迟后除极（发生率６５％）和触发活动,并形成快速自发动作电位。高频刺激时,易产生延迟后除极。外源性组胺（０．６μｍｏｌ／Ｌ和６．０μｍｏｌ／Ｌ）作用于豚鼠心室乳头肌亦产生相似的变化。Ｈ＿２受体阻断剂西咪替丁（１０μｍｏｌ／Ｌ,ｎ＝１０）可明显抑制心性过敏反应和完全阻断组胺所致的延迟后除极现象,Ｈ＿１受体阻断剂扑尔敏（１０μｍｏｌ／Ｌ,ｎ＝６）对心性过敏反应和组胺的效应均无抑制作用。结果提示。心性过敏反应诱发的心肌延迟后除极,可能是心肌释放的组胺直接作用于心室肌Ｈ＿２受体所致。     

川芎嗪对蟾蜍交感神经节细胞膜嘌呤受体介导反应的调制作用

采用细胞外微电极技术,记录离体灌流的蟾蜍椎旁交感神经节细胞膜电位,观察川芎嗪对嘌呤受体介导反应的调制作用。三磷酸腺苷（３００μｍｏｌ／Ｌ）可引起神经节细胞膜去极化（ｎ＝６２）、超极化反应（ｎ＝２７）以及去极化之后伴随超极化过程的双相反应（ｎ＝９）。Ｐ２受体拮抗剂台盼蓝（５００μｍｏｌ／Ｌ）可抑制三磷酸腺苷的去极化反应（ｎ＝８）;Ｐ１受体拮抗剂氨茶碱（２００μｍｏｌ／Ｌ）可抑制三磷酸腺苷的超极化反应（ｎ＝７）。滴加川芎嗪（１～５ｍｍｏｌ／Ｌ）,神经节细胞膜未出现明显的电位变化。外源性环－磷酸腺苷（２５０μｍｏｌ／Ｌ）可模拟三磷酸腺苷的超极化反应（ｎ＝９）。川芎嗪（３ｍｍｏｌ／Ｌ）可抑制三磷酸腺苷的去极化反应,使其幅值减少５３９±９５％（ｎ＝１４,Ｐ＜００１）,并能加强三磷酸腺苷所致超极化反应,使其幅值增大１０５４±２４５％（ｎ＝１２,Ｐ＜００１）。在同一标本上,川芎嗪使环一磷酸腺苷的超极化反应加强（ｎ＝４）。此外,川芎嗪可抑制三磷酸腺苷引起的双相反应中的去极相,而增大其后的超极相（ｎ＝３）。     

4－甲基组胺和三氟啦嗪对WEHI_3细胞增殖的影响

用体外细胞液体培养法研究组胺Ｈ＿２受体激动剂４－甲基组胺（４－ＭＨ）、Ｈ＿２受体拮抗剂西咪替丁和钙调素拮抗剂三氟啦嗪（ＴＦＰ）对小鼠粒单白血病ＷＥＨＩ＿３细胞增殖的影响。结果表明：４－ＭＨ呈剂量依赖性抑制ＷＥＨＩ＿３细胞增殖。１０￣（－４）ｍｏｌ／Ｌ西咪替丁可阻断这种效应。１０￣（－５）─１０￣（－４）ｍｏｌ／ＬＴＦＰ阻断ＷＥＨＩ＿３细胞增殖,１０￣（－６）ｍｏｌ／ＬＴＦＰ对细胞影响不大,但与高浓度４－ＭＨ合用有协同抑制效应。     

组胺H2受体激动剂4—甲基组胺及其拮抗剂雷尼替丁对HL—60白…

在ＨＬ－６０白血病细胞的体外培养中,组胺Ｈ２受体激动剂４－甲基组胺（１０＾－８－１０＾－４ｍｏｌ／Ｌ）对ＨＬ－６０细胞的增殖具有轻微的抑制作用,而组胺Ｈ２受体拮抗剂雷尼替丁（１０＾－８－１０＾－４ｍｏｌ／Ｌ）对ＨＬ－６０细胞的增殖具有较强的抑制作用。但用１０＾－６ｍｏｌ／Ｌ的雷尼替丁预处理ＨＬ－６０细胞则可部分地拮抗４－甲基组胺（１０＾－８－１０＾４ｍｏｌ／Ｌ）对ＨＬ－６０白血病细胞的抑制作用。     

4—甲基组胺和三氟啦嗪对WEHI3细胞增殖的影响

用体外细胞液体培养法研究组胺Ｈ２受体激动剂４－甲基组胺（４－ＭＨ）、Ｈ２受体拮抗剂西咪替丁和钙调素拮抗剂三氟啦嗪（ＴＦＰ）对小鼠粒单白血病ＷＥＨＩ３细胞增殖的影响。结果表明：４－ＭＨ呈剂量依赖性抑制ＷＥＨＩ３细胞增殖。１０＾－４ｍｏｌ／Ｌ西咪替丁可阻断这种效应。１０＾－５－１０＾－４ｍｏｌ／ＬＴＦＰ阻断ＷＥＨＩ３细胞增殖,１０＾－６ｍｏｌ／ＬＴＦＰ对细胞影响不大,但与高浓度４－ＭＨ合用有协同抑制效     

组胺H_2受体激动剂4－甲基组胺及其拮抗剂雷尼替丁对HL－60白血病细胞增殖的作用

在ＨＬ－６０白血病细胞的体外培养中,组胺Ｈ＿２受体激动剂４－甲基组胺（１０￣（－８）－１０￣（－４）ｍｏｌ／Ｌ）对ＨＬ－６０细胞的增殖具有轻微的抑制作用,而组胺Ｈ＿２受体拮抗剂雷尼替丁（１０￣（－８）－１０￣（－４）ｍｏｌ／Ｌ）对ＨＬ－６０细胞的增殖具有较强的抑制作用。但用１０￣（－６）ｍｏｌ／Ｌ的雷尼替丁预处理ＨＬ－６０细胞则可部分地拮抗４－甲基组胺（１０￣（－８）－１０￣（－４）ｍｏｌ／Ｌ）对ＨＬ－６０白血病细胞的抑制作用。     

组胺H_2受体激动剂和拮抗剂对WEHI_3细胞增殖的作用

近年来研究表明组胺及其受体在正常造血调控中起着重要作用。本研究用琼脂半固体培养技术观察了特异性组胺Ｈ２受体激动剂英普咪定和拮抗剂西咪替丁对髓系粒－单核细胞白血病干细胞株ＷＥＨＩ３细胞生长的影响。结果表明不同浓度的英普咪定（１０－８─１０－４ｍｏｌ／Ｌ）对集落数呈明显剂量依赖性抑制,与对照组比较ｐ＜０．０１。１０－１０─１０－９ｍｏｌ／Ｌ英普咪定对集落数无明显影响。１０－４─６×１０－４ｍｏｌ／Ｌ的英普咪定对集落产率的抑制作用趋于饱和。最大抑制效能为对照组的５４％（ｐ＜０．０１）。１０－４ｍｏｌ／Ｌ西咪替丁能完全阻断１０－８ｍｏｌ／Ｌ英普咪定的集落抑制作用。对≥１０－６ｍｏｌ／Ｌ英普咪定的作用西咪替丁均有部分阻断作用,与对照组比较Ｐ＜０．０１。单用西咪替丁对ＷＥＨＩ３细胞无明显直接作用。这提示ＷＥＨＩ３细胞株上存在有组胺Ｈ２受体,激动Ｈ２受体可抑制细胞增殖。     

SNP抑制5-HT诱导的胞内游离钙浓度升高和内钙释放

用Ｆｕｒａ － ２／ＡＭ 荧光测量技术研究了５ － 羟色胺（５－ ＨＴ） 诱导的大鼠尾动脉平滑肌细胞胞内钙升高和一氧化氮（ＮＯ） 的抑制效应。实验表明, 胞外０ｍ ｍｏｌ／ Ｌ Ｃａ２ ＋ 时胞内静息［Ｃａ２ ＋ ］ ｉ 为２０ ．２±８ ．６ｎｍｏｌ／Ｌ（ｎ ＝ ８） 。１０μｍｏｌ／Ｌ ５－ ＨＴ 可诱导出胞内钙库释放引起的瞬态［Ｃａ２ ＋］ｉ 升高,其峰值达２４５ ．７ ±７１．６ｎｍｏｌ／ Ｌ（ｎ ＝ ６） 。１０ － ７ ｍｏｌ／Ｌ 硝普钠（ＳＮＰ） 可抑制５－ ＨＴ 诱导的［Ｃａ２ ＋］ｉ 升高,其峰值浓度降为７５．１±３５ ．９ｎｍｏｌ／Ｌ（ｎ ＝ ５） 。当细胞浴液含２．５ｍ ｍｏｌ／Ｌ Ｃａ２ ＋ 时,静息［Ｃａ２ ＋］ｉ为１１２ ．８ ±１０ ．３ｎｍｏｌ／ Ｌ（ｎ ＝ ５） , 这时１０μｍｏｌ／ Ｌ ５ － ＨＴ 可诱导［Ｃａ２ ＋ ］ ｉ 的峰值为２５２ ．３ ±８０ ．６ｎｍｏｌ／Ｌ（ｎ ＝ ４） ,以及其后平台浓度为１４３ ．０ ±３７ ．６ｎｍｏｌ／Ｌ（ｎ ＝ ４） ,略大于［Ｃａ２ ＋］ｉ 为１１２．８ ±１０ ．３ｎｍｏｌ／Ｌ 的静息浓度,为外钙内流引起。１０ － ７ ｍｏｌ／Ｌ ＳＮＰ 也可抑制５－ ＨＴ 诱导［Ｃａ２ ＋ ］ｉ 平台相浓度。平台浓度由１４３ ±４７     

α受体激动对绵羊心肌瞬时性内向离子流的影响

用乙酰毒毛旋花子甙元（ＡＳ）０．０５μｍｏｌ／Ｌ诱发绵羊心浦肯野纤维产生稳定的瞬时性内向离子流（Ｉｔｉ）,用普萘洛尔０．５μｍｏｌ／Ｌ阻断β受体,观察α受体激动剂苯肾上腺素（ＰＥ）０．３,１．０μｍｏｌ／Ｌ对Ｉｔｉ幅值与时程的影响。ＰＥ１．０μｍｏｌ／Ｌ灌流２０,５０ｍｉｎ时Ｉｔｉ幅值分别由对照值１２．８±１．９ｎＡ减小至１０．７±１．２ｎＡ（ｎ＝５,Ｐ＜０．０５）与９．６±１．９ｎＡ（ｎ＝５,Ｐ＜０．０１）;ＩｔｉＤ５０时程分别由对照值１４５±２４．４ｍｓ延长至１８３．３±２８．１ｍｓ（ｎ＝５,Ｐ＜０．０５）与２０７．５±３４．２ｍｓ（ｎ＝５,Ｐ＜０．０１）,ＰＥ对Ｉｔｉ的抑制作用呈剂量依赖性与时间依赖性。Ｉｔｉ到达峰值的时间和回复到基线的时间都延长,提示ＰＥ作用下Ｉｔｉ通道动力学发生了变化。如果在β受体激动剂异丙肾上腺素（ＩＳＯ）１．０μｍｏｌ／Ｌ增强Ｉｔｉ的基础上,ＰＥ１．０μｍｏｌ／Ｌ灌流１０ｍｉｎ,对Ｉｔｉ幅值的抑制及时程的延长作用更显著,Ｉｔｉ幅值由对照值１５．６±３．２ｎＡ减小到１０．３±２．２ｎＡ;ＩｔｉＤ５０由９２．５±１４．３ｍｓ延长到１３２．５±３６．０ｍｓ（ｎ＝５,Ｐ＜０．０１）。     

α受体激动对绵羊心脏浦肯野纤维延迟后除极的影响

用乙酰毒毛旋花子成元０．２μｍｏｌ／Ｌ诱发绵羊心脏浦肯野纤维产生延迟后除极（ＤＡＤ）,采用细胞内微电极记录。在用普奈洛尔１．０μｍｏｌ／Ｌ阻断β受体条件下,苯肾上腺素１．０μｍｏｌ／Ｌ使ＤＡＤ幅值由８．１±２．２ｍＶ增至９．５±２．８ｍＶ,时程由２４０±４７ｍｓ延长到２７３±４７ｍｓ（ｎ＝１３,ＰＭ＜０．０１）,ＤＡＤ上升速率由０．０３９±０．０２３Ｖ／ｓ增至０．０５１±０．０２６Ｖ／ｓ（ｎ＝１３,Ｐ＜０．０５）,ＤＡＤ在动作电位后出现的时间提前了３０±４７ｍｓ（ｎ＝１３,Ｐ＜０．０５）。用去甲肾上腺素１．０μｍｏｌ／Ｌ增强ＤＡＤ引起触发活动时,酚妥０拉明１．８μｍｏｌ／Ｌ不能抑制触发活动,普奈洛尔１．０μｍｏｌ／Ｌ能抑制之。上述结果表明α受体激动对ＤＡＤ有轻度增强作用,但由ＤＡＤ引起的触发活动,α受体阻滞剂的抑制作用不如β受体阻滞剂有效。     

Histamine excites rat cerebellar granule cells in vitro through H1 and H2 receptors.

The effects of histamine on the firing of cerebellar granule cells were investigated in vitro. Histamine predominantly produced excitatory (117/123, 95.1%) and in a few cases inhibitory (6/123, 4.9%) responses in granule cells. The histamine-induced excitation was not blocked by perfusing the slice with low Ca2+/high Mg2+ medium, supporting a direct postsynaptic action of histamine. The H1 receptor antagonists triprolidine and chlorpheniramine significantly diminished the histamine-induced excitation, but the H2 receptor antagonist ranitidine did not significantly reduce the excitation. On the other hand, the H2 receptor agonist dimaprit could elicit a weak excitation of granule cells. This dimaprit-induced excitation was blocked by ranitidine but not triprolidine. These results reveal that the excitatory effect of histamine on cerebellar granule cells is mediated by both H1 and H2 receptors with a predominant contribution of H1 receptors. The relevance of these findings to the possible function of the hypothalamocerebellar histaminergic fibers in cerebellum is discussed.     

Terfenadine induces toxicity in cultured cerebellar neurons: A role for glutamate receptors

Summary Exposure of cultured cerebellar neurons to the histamine H1 receptor antagonist terfenadine resulted in neuronal degeneration and death. Terfenadine neurotoxicity was dependent upon concentration and time of exposure. After 2h exposure, 20µM terfenadine reduced the number of surviving neurons by 75%, and as low as 10nM terfenadine induced significant neurotoxicity after 5 days of exposure. Neuronal sensitivity to terfenadine changed with age in culture, and at 25 days in culture neurons appeared to be much less sensitive than at 5 or 9–17 days in culture. Neurotoxicity by terfenadine could not be prevented by high concentrations of histamine (5 mM), but it was significantly delayed by blocking NMDA or non-NMDA glutamate receptors with MK-801 or CNQX respectively, suggesting the involvement of excitatory transmission mediated by glutamate in the neurotoxicity induced by terfenadine in these neurons. We also found that the presence of terfenadine (5,µM) unveiled the potential excitotoxicity of the non-NMDA receptor agonist AMPA (100µM), and reduced the concentration of glutamate necessary to induce excitotoxicity, compared to untreated cultures. These results suggest a role for terfenadine in the modulation of the excitotoxic response mediated in cerebellar neurons through ionotropic glutamate receptors.     

Actions of histamine on muscle and ganglia of the guinea pig gallbladder

Histamine is an inflammatory mediator present in mast cells, which are abundant in the wall of the gallbladder. We examined the electrical properties of gallbladder smooth muscle and nerve associated with histamine-induced changes in gallbladder tone. Recordings were made from gallbladder smooth muscle and neurons, and responses to histamine and receptor subtype-specific compounds were tested. Histamine application to intact smooth muscle produced a concentration-dependent membrane depolarization and increased excitability. In the presence of the H(2) antagonist ranitidine, the response to histamine was potentiated. Activation of H(2) receptors caused membrane hyperpolarization and elimination of spontaneous action potentials. The H(2) response was attenuated by the ATP-sensitive K(+) (K(ATP)) channel blocker glibenclamide in intact and isolated smooth muscle. Histamine had no effect on the resting membrane potential or excitability of gallbladder neurons. Furthermore, neither histamine nor the H(3) agonist R-alpha-methylhistamine altered the amplitude of the fast excitatory postsynaptic potential in gallbladder ganglia. The mast cell degranulator compound 48/80 caused a smooth muscle depolarization that was inhibited by the H(1) antagonist mepyramine, indicating that histamine released from mast cells can activate gallbladder smooth muscle. In conclusion, histamine released from mast cells can act on gallbladder smooth muscle, but not in ganglia. The depolarization and associated contraction of gallbladder smooth muscle represent the net effect of activation of both H(1) (excitatory) and H(2) (inhibitory) receptors, with the H(2) receptor-mediated response involving the activation of K(ATP) channels.     

Histamine Stimulation of Inositol 1-Phosphate Accumulation in Lithium-Treated Slices from Regions of Guinea Pig Brain

Histamine stimulated the accumulation of [3H]inositol 1-phosphate in the presence of 10 mM LiCl in [3H]inositol-loaded tissue slices from several regions of guinea pig brain. The level of [3H]inositol 1-phosphate increased approximately linearly, after an initial lag period, up to a time of 120 min. In the absence of lithium ions the accumulation of the 1-phosphate stimulated by histamine in cerebral cortical and hippocampal slices was markedly reduced. Lithium ions had much less effect on the response to histamine in cerebellar slices. The characteristics of the response to histamine were consistent with mediation by H1 receptors, and the affinity constants derived for mepyramine (2.3 X 10(9) M-1) and methapyrilene (1.8 X 10(8) M-1) were similar to those reported from measurements on other H1 responses in the guinea pig. The EC50 for histamine was similar in cerebellum, cerebral cortex, hippocampus, and hypothalamus. The position of the dose-response curve for histamine in cerebral cortical slices was similar to that of the curve for the receptor binding of histamine deduced from histamine inhibition of [3H]mepyramine binding.     

Synaptic responses evoked by tactile stimuli in Purkinje cells in mouse cerebellar cortex Crus II in vivo

Background

Sensory stimuli evoke responses in cerebellar Purkinje cells (PCs) via the mossy fiber-granule cell pathway. However, the properties of synaptic responses evoked by tactile stimulation in cerebellar PCs are unknown. The present study investigated the synaptic responses of PCs in response to an air-puff stimulation on the ipsilateral whisker pad in urethane-anesthetized mice.

Methods and Main Results

Thirty-three PCs were recorded from 48 urethane-anesthetized adult (6–8-week-old) HA/ICR mice by somatic or dendritic patch-clamp recording and pharmacological methods. Tactile stimulation to the ipsilateral whisker pad was delivered by an air-puff through a 12-gauge stainless steel tube connected with a pressurized injection system. Under current-clamp conditions (I = 0), the air-puff stimulation evoked strong inhibitory postsynaptic potentials (IPSPs) in the somata of PCs. Application of SR95531, a specific GABA_A receptor antagonist, blocked IPSPs and revealed stimulation-evoked simple spike firing. Under voltage-clamp conditions, tactile stimulation evoked a sequence of transient inward currents followed by strong outward currents in the somata and dendrites in PCs. Application of SR95531 blocked outward currents and revealed excitatory postsynaptic currents (EPSCs) in somata and a temporal summation of parallel fiber EPSCs in PC dendrites. We also demonstrated that PCs respond to both the onset and offset of the air-puff stimulation.

Conclusions

These findings indicated that tactile stimulation induced asynchronous parallel fiber excitatory inputs onto the dendrites of PCs, and failed to evoke strong EPSCs and spike firing in PCs, but induced the rapid activation of strong GABA_A receptor-mediated inhibitory postsynaptic currents in the somata and dendrites of PCs in the cerebellar cortex Crus II in urethane-anesthetized mice.     

Effects of H1 and H2 receptor antagonists on Tetrahymena.

In Tetrahymena pyriformis the phagocytotic rate increases in response to histamine, but neither the H1 antagonist phenindamine nor the H2 antagonist metiamide stimulate phagocytosis. The H1 antagonist counteracts the effect of histamine, whereas the H2 antagonist does not. The histamine receptor of Tetrahymena is of H1-type, since it cannot distinguish between histamine and antagonists which are closely related to it chemically. It does, however, distinguish between histamine and the chemically unrelated H1 antagonist, phenindamine. The H2 antagonist does not interact with the receptor.     

Inositol Phospholipid Hydrolysis in Rat Cerebral Cortical Slices: I. Receptor Characterisation

Characterisation of receptor-mediated breakdown of inositol phospholipids in rat cortical slices has been performed using a direct assay which involves prelabelling with [3H]inositol. When slices were preincubated with [3H]inositol, lithium was found to greatly amplify the capacity of receptor agonists such as carbachol, noradrenaline, and 5-hydroxytryptamine to increase the amount of radioactivity appearing in the inositol phosphates. Using a large variety of agonists and antagonists it could be shown that cholinergic muscarinic, alpha 1-adrenoceptor, and histamine H1 receptors appear to be linked to inositol phospholipid breakdown in cortex. The large responses produced by receptor agonists allowed a clear discrimination between full and partial agonists as well as quantitative analysis of competitive antagonists for each receptor. Whereas carbachol and acetylcholine (in the presence of a cholinesterase inhibitor) were full agonists, oxotremorine and arecoline were only partial agonists. Very low concentrations of atropine shifted the carbachol dose-response curve to the right and allowed inhibition constants for the antagonist to be easily calculated. The nicotinic antagonist, mecamylamine, was ineffective. Noradrenaline adrenaline were full agonists at alpha 1-adrenoceptors, but phenylephrine and probably methoxamine were partial agonists. Prazosin, but not yohimbine, potently and competitively antagonised the noradrenaline inositol phospholipid response. Mepyramine but not cimetidine competitively antagonised the histamine response. These data provide strong confirmation for the potentiating effect of lithium on neurotransmitter inositol phospholipid breakdown and emphasise the ease with which functional responses at a number of cortical receptors can be characterised.     

电刺激大鼠巨细胞网状核对小脑浦肯野细胞自发和诱发电活动的影响

本研究在麻醉并制动的大鼠上观察了电刺激巨细胞网状核(Gi)对小脑浦肯野细胞(PC)自发及诱发简单锋电位的影响。结果如下:(1)刺激Gi可使PC的简单锋电位出现潜伏期小于20ms的抑制性或兴奋性反应,并以抑制性反应为主。抑制性反应持续40-100ms,而兴奋性反应的时程可达200ms以上;(2)注射5-HT_2型受体阻断剂methysergide可以减弱或阻断电刺激Gi对PC自发简单锋电位的抑制作用;(3)条件性Gi刺激可以显著压抑或加强由刺激对侧大脑皮层感觉运动区引起的PC诱发简单锋电位反应。以上结果说明:在大鼠存在Gi-小脑通路,这一通路中的部分纤维是5-HT能的。Gi-小脑纤维可能通过突触和/或非经典突触的化学传递方式对PC的电活动产生某种调制性的影响。推测Gi-小脑传入纤维投射可能在某些小脑功能活动,如肌紧张及姿势的调节等方面发挥重要作用。     

Histamine modulates local inhibition in the rat hippocampal slice

1. These experiments investigated the action of histamine on local inhibition in the CA1 region of the in vitro hippocampal slice preparation using a paired-pulse paradigm. 2. We observed that histamine produced a concentration-dependent and reversible attenuation of paired-pulse inhibition. This effect was reduced by the H2 receptor antagonist, cimetidine, and mimicked by the H2 receptor agonist, impromidine. 3. We also observed that histamine produced concentration-dependent effects on the amplitude of the population spike that could be correlated with alterations in the field excitatory postsynaptic potential (EPSP) amplitude and input fiber volley. High concentrations of histamine produced a reduction in the amplitude of the population spike which was always accompanied by a reduction in the EPSP and fiber volley amplitude. 4. These results suggest that histamine, through the occupancy of H2 receptors, acts to modulate the efficacy of the local synaptic circuitry which is involved in producing paired-pulse inhibition in the hippocampus.     

Action of histamine on the rapidly adapting airway receptors in the dog

The effects of histamine on the activity of rapidly adapting receptors (RAR) of the airways were investigated in anesthetized dogs. With bolus injections given into the right atrium, the threshold dose of histamine required for the excitation of RAR (n = 7) was 0.82 microgram/kg (+1.33/-0.51, geometric mean). With increasing doses of histamine, a dose-response relationship was seen in the activity of RAR. Obstruction of the lymphatic drainage from the lungs reduced the threshold dose to histamine (i.e., shifted the dose-response curve to the left significantly). This change in the dose-response relationship was not accompanied by a corresponding change in the relationship of histamine dose to airway pressures recorded before and after lymphatic obstruction. Against a background of pulmonary venous congestion produced by partial obstruction of the mitral valve, subthreshold doses of histamine stimulated the RAR (n = 4). The excitatory effect of histamine on RAR was found to be abolished by the administration of the H1 receptor antagonist diphenhydramine but not by the H2 receptor antagonist cimetidine. Intravenous infusion of histamine (0.4 microgram.kg-1.min-1) for a period of 10 min increased the RAR activity (n = 6) significantly without producing detectable changes in airway mechanics. The results indicate that contraction of the smooth muscle of the airways may not be a prerequisite for the excitation of RAR, especially at low doses. It is suggested that some of the effects of histamine on RAR are mediated by a local expansion of the extravascular fluid caused by an increase in the permeability of the bronchial vasculature.