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B J Undem

Publications and source records attributed to B J Undem.

At least 91 records · Page 5Linked to original sources
PubMed1992

Antigen-induced enhancement of noncholinergic contractile responses to vagus nerve and electrical field stimulation in guinea pig isolated trachea.

Nonadrenergic, noncholinergic contractions were elicited by electrical field stimulation (EFS) (2 Hz, 1 msec, 12 V for 15 sec) of the distal aspect of guinea pig trachea pretreated with atropine (1 microM), propranolol (1 microM) and indomethacin (3 microM). The contractions were abolished by pretreatment with the sensory C-fiber toxin capsaicin or by a combination of the neurokinin (NK)1 receptor antagonist, CP 96,345 (0.1 microM), and the NK2 receptor antagonist, MEN 10376 (3 microM), and were markedly attenuated by tetrodotoxin. In animals actively sensitized to ovalbumin, the addition of threshold concentrations of antigen markedly increased the noncholinergic contractile responses to EFS (approximately 3- to 6-fold). This potentiation was long lasting, persisting virtually unchanged for 60 min, whereas the antigen-induced contractions were shorter lived, usually lasting less than 30 min. The ovalbumin-induced potentiation of the neuronal response was not observed in tissues pretreated with capsaicin or treated with tetrodotoxin. This antigen-induced potentiation of capsaicin-sensitive, EFS-induced contractions was not mimicked by serotonin or prostaglandin D2. However, it was mimicked by histamine. Moreover, the histamine H1 receptor antagonist pyrilamine (0.3 microM) reversed the potentiation elicited by ovalbumin. The effect of ovalbumin challenge was also examined on the distal trachea with the right vagus nerve intact. Noncholinergic contractions to EFS and vagus nerve stimulation were enhanced equally by threshold concentrations of antigen. The results support the hypothesis that antigen challenge releases histamine which acts via H1 receptors to enhance noncholinergic contractions due to the release of tachykinins from capsaicin-sensitive fibers in the guinea pig trachea.

Animals↗
PubMed1991

Dynamics of platelet-activating-factor release and uptake in a human neutrophil suspension.

The present study has examined the dynamics of platelet-activating-factor (PAF) synthesis, release and uptake in order to understand better the trafficking of PAF between cells and medium. Initial experiments indicated that the amount of PAF found on the outside of the cell remained constant well after the synthesis from a precursor had apparently stopped, and in spite of a continued capacity of the cell to take up and catabolize PAF. These results suggested that PAF produced and stored within the cell is eventually released to the outside of the cell at a rate proportional to that of cellular uptake. In order to estimate the amount of PAF released from the cell, the processes of PAF release and uptake were modelled using simple mathematical functions. It was found that, under the experimental conditions used in this study, the uptake of PAF could be expressed as an exponential function tending to a non-zero baseline. Utilizing this rate constant for the uptake of PAF with the amount of PAF outside the cell, the amount of total PAF released from the cell was estimated. Data from the model suggested PAF was released in amounts 10-fold higher than could actually be measured over 30 min. In fact, the model predicted more PAF could be released from the cell than is synthesized, suggesting that a portion of the PAF which is released is taken up and then released again to the outside of the cell. The potential for PAF and/or its intermediates to be recycled was verified by demonstrating that a large proportion of exogenously provided 1-alkyl-2-lyso-sn-glycero-3-phosphocholine is taken up by the neutrophil, converted into PAF and then released again by the cell. These results suggest that PAF trafficking between the cell and medium is complex and involves many processes, which include synthesis, release, uptake, catabolism and recycling.

Calcimycin↗
PubMed1991

Analysis of preganglionic nerve evoked cholinergic contractions of the guinea pig bronchus.

We compared cholinergic bronchial muscle contractions induced by vagus nerve (preganglionic) stimulation (VNS) with those induced by electrical field (postganglionic) stimulation (EFS). When normalized to their respective maximum response, the frequency-response curves (10 s trains) between 4 and 16 Hz were similar between VNS and EFS; however, at frequencies of 0.1-2 Hz, and at frequencies greater than 32 Hz, the VNS contractions were significantly less than EFS. When contractions elicited by 100 pulses were examined, it was found that the responses to VNS were maximal at 10-30 Hz then declined significantly to 82-35% of maximal between 40 and 200 Hz, whereas the response to EFS was essentially unchanged at frequencies up to 60 Hz and declined only to 72% of maximal up to 200 Hz. At frequencies as low as 20 Hz, the contractions evoked by VNS faded to 45 +/- 9% of the peak contraction during 60 sec of continuous stimulation, whereas those evoked by 60 sec continuous EFS remained constant. This fade observed during prolonged VNS was not blocked by the antagonists, pirenzepine and AFDX-116, at concentrations selective for M1 and M2 muscarinic receptors, respectively; nor was the fade blocked by pre-treatment with indomethacin, propranolol, phentolamine, or choline. At frequencies greater than 10 Hz, the amplitude of the preganglionic compound action potential also faded during repetitive stimulation. The results support the hypothesis that the airway ganglion neurons innervating guinea pig bronchial smooth muscle effectively filter preganglionic stimuli, especially at low and relatively high frequencies. During continuous vagus nerve stimulation, preganglionic mechanisms may also play a role in limiting the ultimate output of airway ganglia.

Animals↗
PubMed1991

Role of peptidoleukotrienes in capsaicin-sensitive sensory fibre-mediated responses in guinea-pig airways.

1. The right bronchus with the right vagus nerve remaining intact was isolated from the guinea-pig. Stimulating the end of the right vagus nerve distal to the bronchus resulted in a biphasic contractile response with a rapid first phase and a second phase which persisted after the cessation of stimulation. The first phase was selectively sensitive to atropine, while the second phase was non-cholinergic, but abolished by pre-treatment with the sensory C fibre toxin, capsaicin. This biphasic contraction was mimicked by electrical field stimulation of the bronchus and strips of the distal aspect of the trachea. 2. The capsaicin-sensitive second phase produced by either vagus nerve stimulation or electrical field stimulation, was inhibited by greater than 50% by the selective peptidoleukotriene receptor antagonist SKF 104353, whereas the inactive stereoisomer of SKF 104353, SKF 104373, was without effect. SKF 104353 did not inhibit the cholinergic first phase, nerve conduction along the vagus nerve, or contractions to exogenously added substance P and neurokinin A. 3. The inhibitory effect of SKF 104353 on second-phase contractions was mimicked by two structurally unrelated selective peptidoleukotriene receptor antagonists, WY 48252 and ICI 198615, and by the 5'-lipoxygenase inhibitor REV 5901. 4. Exogenously added leukotriene D4 (1 nM) potentiated the second-phase contractions in the trachea and this effect was reversed by 0.1 microM-SKF 104353. Leukotriene D4 did not affect responses to exogenously added substance P or neurokinin A. 5. Stimulation of the right vagus nerve produced plasma extravasation in the trachea and in the main bronchi of atropine- and propranolol-pre-treated guinea-pigs. This was inhibited by about 50% by SKF 104353 (10 mg/kg, I.V.), whereas SKF 104373 (10 mg/kg, I.V.) was without effect. 6. It is suggested that endogenous peptidoleukotrienes make a significant contribution to the airway smooth muscle and vascular effects of capsaicin-sensitive nerve stimulation in the guinea-pig.

Animals↗
PubMed1991

Influence of antigen on membrane properties of guinea pig bronchial ganglion neurons.

The bronchus was isolated from actively sensitized guinea pigs, and the effect of antigen challenge on the excitability of bronchial parasympathetic ganglion neurons was examined with standard intracellular recording techniques. Based on histological examination, we found that mast cells were located near parasympathetic ganglia neurons. Antigen challenge resulted in a loss of mast cell staining and the release of the mast cell-associated mediators, histamine (38 ng/g, approximately 14% of total content) and prostaglandin D2 (PGD2, 118 ng/g wet weight of tissue). Challenging the isolated bronchus with the sensitizing antigen resulted in a transient depolarization (mean 6 mV) of the resting membrane potential of the neurons. Antigen challenge also had a dramatic effect on the accommodative properties of the neurons. Before antigen challenge, two subpopulations of neurons could be differentiated by their response to cathodal current steps: 60% of the cells responded in a "phasic" manner, firing one to six spikes and then accommodated, whereas the balance fired spikes repetitively throughout the current pulse. In phasic firing cells, ovalbumin challenge produced a decrease in accommodation. This was evidenced by a fivefold increase in the number of action potentials elicited during a 500-ms suprathreshold current pulse. The antigen-induced depolarization could be mimicked by histamine, whereas the decrease in accommodation was mimicked by application of PGD2. Leukotriene C4, another mast cell-associated mediator, had no effect on these neuronal properties. These results provide evidence that the immediate hypersensitivity response in guinea pig airways may involve changes in membrane characteristics of bronchial parasympathetic ganglia neurons.

Action Potentials↗
PubMed1991

Antigen-induced modulation of autonomic and sensory neurons in vitro.

We have addressed the hypothesis that the excitability of peripheral neurons is affected during immediate hypersensitivity reactions. Guinea pigs were actively sensitized to ovalbumin. The electrical membrane properties of neurons within the superior cervical ganglion, bronchial parasympathetic ganglion and nodose ganglion were evaluated before, during and after antigen challenge. In all preparations, antigen stimulation induced the release of histamine and arachidonic acid metabolites. Our results support the hypothesis that the excitability of sympathetic, parasympathetic and sensory C-type neurons may be increased during immediate hypersensitivity reactions.

Action Potentials↗
PubMed1991

Functional interactions between capsaicin-sensitive and cholinergic nerves in the guinea pig bronchus.

Electrical stimulation of the right vagus nerve causes a biphasic contraction of the guinea pig isolated right bronchus. The "first-phase" is blocked by hexamethonium or atropine and the "second-phase" is eliminated by capsaicin pretreatment. We investigated a potential interaction between capsaicin-sensitive nerves and cholinergic nerves in the guinea pig bronchus. Hexamethonium (100 microM) abolished the first-phase contraction but had no effect on the capsaicin-sensitive second-phase contraction. In the presence of hexamethonium, atropine (0.1 microM) significantly decreased the amplitude of the second-phase contraction by 28%. Similar results were observed with the M3-selective muscarinic receptor antagonist, 4-diphenyl-acetoxy-M-methylpipe-radine, but not with the M2 muscarinic antagonist, AFDX-116. Atropine also reduced contractions induced by exogenously applied neurokinin A. We then analyzed the effect of stimulating capsaicin-sensitive fibers with electrical field stimulation on vagus nerve evoked cholinergic contractions. By reducing the stimulus intensity we were able to evoke vagus nerve-mediated contractions that were exclusively cholinergic in nature. The cholinergic contractions were significantly increased after stimulation of capsaicin-sensitive fibers by about 50%. By contrast, contractions elicited by exogenous methacholine were unaffected after field stimulation of capsaicin-sensitive responses. Our findings indicate that the contractions of the guinea pig bronchus elicited by stimulation of capsaicin-sensitive nerves are due in part to muscarinic cholinergic receptor activation. Secondly, our data demonstrate that the cholinergic contractions elicited by vagal preganglionic nerve stimulation are potentiated by neurotransmitter(s) released from capsaicin-sensitive fibers in bronchus.

Animals↗
PubMed1990

Inhibition by adenosine 3':5'-monophosphate of eicosanoid and platelet-activating factor biosynthesis in the mouse PT-18 mast cell.

A mouse spleen-derived mast cell line (PT-18) was employed to examine the mechanisms of adenosine 3':5'-monophosphate (cAMP)-mediated inhibition of antigen-induced lipid mediator biosynthesis. Specifically, we tested the hypothesis that increasing cAMP in mast cells inhibits lipid mediator biosynthesis by a mechanism independent of effects on histamine release (degranulation) or changes in cytosolic calcium concentration. Forskolin inhibited antigen-induced prostaglandin D2 (PGD2), leukotriene C4 (LTC4), and leukotriene B4 (LTB4) production by 30-50%. In contrast, forskolin had no inhibitory effect on antigen-induced increases in cytosolic calcium concentration, as monitored by the calcium indicator fura-2, or histamine release from the cells. The combination of the phosphodiesterase inhibitor isobutylmethylxanthine with forskolin inhibited the antigen-induced production of PGD2 and LTC4 by 90-100% and histamine release by about 60%. These responses were accompanied by a virtual abolition of the antigen-induced increase in cytosolic calcium. To test further the hypothesis that increasing cAMP can lead to inhibition of lipid mediator biosynthesis in the absence of effects on cytosolic calcium, we employed the calcium ionophores A23187 and ionomycin. Forskolin alone or in combination with isobutylmethylxanthine had no effect on ionophore-induced increases in cytosolic calcium but effectively inhibited leukotriene biosynthesis. In addition, increasing cyclic AMP led to an inhibition of ionophore-induced production of platelet-activating factor and liberation of arachidonic acid. These data suggest that a relatively modest increase in cAMP-dependent protein kinase activity in mast cells leads to inhibition of the lipase-catalyzed cleavage of arachidonic acid from membrane phospholipids in the absence of measurable effects on either histamine release or changes in cytosolic calcium concentration. This effect results in a selective inhibition of the biosynthesis of lipid mediators including LTC4, LTB4, PGD2, and platelet-activating factor.

1-Methyl-3-isobutylxanthine↗
PubMed1990

Mast cells in the guinea pig superior cervical ganglion: a functional and histological assessment.

We have previously found that antigenic stimulation of mast cells in the guinea pig superior cervical ganglion leads to membrane depolarization of principal neurons and a long-term increase in the efficacy of ganglionic transmission. In this study experiments were conducted to discern the histological, immunological and pharmacological characteristics of the mast cells within the superior cervical ganglion. Mast cells within the superior cervical ganglion could be stained with toluidine blue or berberine sulfate, the latter indicating that heparin-like molecules were present in the granules. Stainable mast cells were distributed throughout the ganglion with no gross evidence of regional localization. The number of mast cells stained with toluidine blue was reduced significantly (P less than 0.01) in contralateral ganglia that had been exposed to the sensitizing antigen (ovalbumin), indicating antigen-induced degranulation. The superior cervical ganglion contained 208 +/- 6 picomole of histamine (mean +/- SEM, n = 66). Ovalbumin evoked the release of histamine from the superior cervical ganglion in a concentration-dependent fashion. At maximally effective concentrations, ovalbumin released 33 +/- 2% of the total histamine stores (mean +/- SEM, n = 61). Similar values were obtained with antigen-challenged stellate ganglia. A temperature of 37 degrees C and an extracellular calcium concentration of 1 mM was required to elicit optimal antigen-induced responses. In addition to releasing histamine, antigenic stimulation of the ganglion resulted in a 3- to 5-fold increase in the synthesis and release of arachidonic acid metabolites including peptidoleukotriene, thromboxane B2, prostaglandins (PG) E2, F2 alpha, D2, the PGD2 metabolite 9 alpha 11 beta-PGF2, and the prostacyclin metabolite 6-keto PGF1 alpha. Various putative mast cell secretagogues were examined for their ability to activate the superior cervical ganglion mast cell, as indicated by evoked histamine release. In contrast to rat peritoneal mast cells, high concentrations of substance P, compound 48/80, and nerve growth factor failed to stimulate the ganglion mast cells. Preganglionic nerve stimulation, electrical field stimulation of axons and cell bodies, or depolarizing concentrations of potassium chloride also failed to activate the superior cervical ganglion mast cells. These results suggest that substances released by membrane depolarization do not influence the function of the resident mast cells. The results demonstrate that the mast cells within sympathetic ganglia can be actively sensitized to respond to specific antigen. These mast cells are similar to lung parenchymal mast cells with respect to histological, immunological and pharmacological characteristics...

Animals↗
PubMed1990

Non-adrenergic, non-cholinergic contractions in the electrically field stimulated guinea-pig trachea.

1. The effects of drugs and altering stimulus parameters on neurogenic responses to electrical field stimulation (EFS) have been investigated in distal and proximal portions of the guinea-pig trachea. 2. In the presence of indomethacin (3 microM) and propranolol (1 microM) two contractile phases were evident in both the proximal and distal trachea. The first rapid phase was abolished by atropine (0.1 microM), whereas the prolonged, second phase was abolished by capsaicin (10 microM) pretreatment. Tetrodotoxin (3 microM) abolished the initial response and greatly inhibited the second phase. In proximal trachea this second phase was evident only in 9 of 22 preparations. The addition of the peptidase inhibitor thiorphan (10 microM) however, caused a second phase to be seen in all the proximal tissues examined. 3. The two phases of the contractions to EFS were differentially sensitive to the pulse duration applied. The initial, cholinergic contractions were evident at lower pulse durations than were the prolonged capsaicin-sensitive contractions, with the first phase being approximately 10 fold more sensitive than the second phase. 4. The magnitude of the capsaicin-sensitive contraction to EFS was significantly greater in the distal trachea than in the proximal trachea. This difference prevailed in the presence of thiorphan, an inhibitor of neutral endopeptidase. In contrast, concentration-response curves to capsaicin were similar in segments of proximal and distal trachea. 5. The non-adrenergic non-cholinergic (NANC) relaxant responses were studied in tissues in which excitatory neurogenic responses were pharmacologically abolished by capsaicin and atropine treatment. The NANC relaxant responses in the proximal trachea were evident at lower pulse frequencies and were of greater magnitude compared with NANC relaxant responses in the distal trachea. 6. These results indicate that, by pharmacologically manipulating the trachea and by selecting optimum stimulation parameters, a NANC contractile response to EFS can be seen throughout the length of the guinea-pig trachea. This NANC response is most likely to be due to the release of tachykinins from capsaicin-sensitive sensory fibres. It is suggested that NANC relaxant responses mask NANC contractile responses especially in the proximal trachea where NANC relaxant responses predominate.

Animals↗
PubMed1990

Electrophysiological properties of neurons in guinea pig bronchial parasympathetic ganglia.

Active and passive membrane membrane properties of parasympathetic neurons were examined in vitro in a newly localized ganglion on the right bronchus of the guinea pig. Neurons could be classified as "tonic" or "phasic" based on their action potential discharge response to suprathreshold depolarizing constant current steps. Tonic neurons (39%) responded with repetitive action potentials sustained throughout the current step, whereas phasic neurons (61%) responded with an initial burst of action potentials at the onset of the step but then accommodated. Tonic and phasic neurons could not be differentiated by other active or passive membrane properties. Electrical stimulation of the vagus nerve elicited one to three temporally distinct fast nicotinic excitatory potentials, and tetanic stimulation of the vagus nerve evoked slow depolarizing (10% of neurons) and hyperpolarizing (25% of neurons) potentials; the latter was mimicked by muscarinic receptor activation. Similar slow and fast postsynaptic potentials were observed in both tonic and phasic neurons. We suggest neurons within the bronchial ganglion possess membrane and synaptic properties capable of integrating presynaptic stimuli.

Action Potentials↗
PubMed1990

Vagal innervation of guinea pig bronchial smooth muscle.

We isolated the guinea pig right bronchus with the vagus nerves intact and evaluated the changes in isometric tension of the smooth muscle in response to nerve stimulation. Brief (10-s) trains of electrical field stimulation or vagus nerve stimulation caused a biphasic contraction: the "first phase" sensitive to atropine and the "second phase" sensitive to capsaicin. The two phases could be dissociated by adjusting the stimulus intensity; greater stimulus intensities (pulse durations or voltage) were required to evoke the capsaicin-sensitive phase. When stimulated at 30-min intervals, the magnitude of both phases of the contractions declined over a 2-h period of repeated stimulation; however, this was prevented by indomethacin. Stimulation of the left vagus nerve resulted in a monophasic contraction of the right bronchus, with little evidence of a capsaicin-sensitive phase. Blocking neurotransmission through the bronchial ganglion, as monitored by intracellular recording techniques, abolished the first-phase contraction but had no effect on the capsaicin-sensitive phase. Selective blockade of muscarinic M1 receptors had no effect on vagus nerve-mediated contractions. The results demonstrate that the left and right vagus nerves carry preganglionic fibers to the right bronchial ganglion. The right but not the left vagus nerve also carries capsaicin-sensitive afferent fibers that, when stimulated, result in a persistent contraction of the right bronchus. Finally, we provide functional and electrophysiological evidence supporting the hypothesis that capsaicin-sensitive afferent neurons communicate with postganglionic motoneurons within the bronchus.

Animals↗
PubMed1990

Histamine acting on a histamine type 1 (H1) receptor increases beta-glucuronidase release from human lung macrophages.

The effects of histamine on lung macrophages have been studied by both biologic and radioligand experiments. After overnight adherence, lung macrophages spontaneously released beta-glucuronidase (beta-G) at a rate of approximately 7 nmol of hydrolyzed substrate/h/million cells. Histamine at low concentrations (10(-9) to 10(-8) M) resulted in a consistent potentiation of this release. The concentration-effect curve of histamine was bell-shaped, reaching an optimum at 10(-9) M, with concentrations greater than 10(-8) M having no significant effect. At a maximally effective concentration (10(-9) M), histamine evoked a 135 +/- 9.6% (mean +/- SE; n = 8, P less than 0.001) potentiation in the total amount of beta-G released during the first 60 min of incubation. This increase in beta-G release represented both a slight increase in beta-G synthesis as well as an increase in the percentage of beta-G released. When the secreted beta-G is expressed as a percentage of total content, histamine (10(-9) M) evoked a 125 +/- 3.2% (mean +/- SE; n = 27, P less than 0.0005) enhancement. The potentiation of beta-G release by histamine was evident after 45 min of incubation and persisted for up to 6 h. The potentiation of beta-G by histamine was sensitive to inhibition by pyrilamine (10(-7) M).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Release of platelet-activating factor and the metabolism of leukotriene B4 by the human neutrophil when studied in a cell superfusion model.

Stimulated human neutrophils are known to synthesize large quantities of 1-0-alkyl-2-acetyl-sn-glycero-3-phosphocholine (PAF) and 5,12-dihydroxy-6,14-cis-8,10-trans-transeicosatetraenoic acid (LTB4). However, in an isolated cell suspension the majority of synthesized PAF appears to remain cell associated. In addition, LTB4 is rapidly metabolized to an omega-oxidation product (20-OH-LTB4). Experiments were designed to test the hypothesis that the degree of association of PAF with the neutrophils and the metabolism of LTB4 by the neutrophils is a result of the in vitro condition used during cell activation. Here we have compared in paired experiments ionophore A23187-induced production of PAF and LTB4 by human neutrophils in a concentrated cell suspension, a diluted cell suspension and in a system in which the cells are placed on a matrix and superfused with buffer at a constant flow rate (dynamic system). There was little difference in the amount of PAF synthesized in the concentrated cell suspension and the dynamic system. However, less PAF was produced by neutrophils in the dilution system. The percent of PAF released was consistently greater in the dynamic and dilution systems than in the concentrated cell suspension. For example, more than 40% of PAF measured by incorporation of [3H]acetate or gas chromatography/mass spectrometry was released in the dynamic system and dilution systems. In contrast, less than 15% of the PAF synthesized was released from the cells in the concentrated cell suspension. 1-0-Hexadecyl-2-acetyl-3-GPC was primarily released from the neutrophils. By contrast both 1-0-hexadecyl and 1-0-octadecyl linked species of PAF were found within the cells. Exogenous PAF added to neutrophils in the dynamic or dilution systems was taken up and metabolized at a significantly lower rate than that added to cells in the concentrated cell suspension. Most of the leukotrienes synthesized by the neutrophil during A23187 stimulation were released from the cells. However, studies of LTB4 metabolism revealed differences between the dynamic and concentrated cell suspension designs. By 20 min, most of the LTB4 was recovered as 20-OH-LTB4 in the concentrated cell suspension, whereas in the dynamic system little 20-OH-LTB4 was found in the superfusate over 20 min. These experiments suggest that a large proportion of PAF synthesized by neutrophils may be released. They also suggest that the omega-hydroxylation of LTB4 by neutrophils occurs after synthesized LTB4 is released and taken back up by the cell.

Acetates↗
PubMed1989

Endogenous histamine excites neurones in the guinea-pig superior cervical ganglion in vitro.

1. Intracellular recordings were obtained from neurones in the guinea-pig superior cervical ganglion (SCG) in vitro to study the electrophysiological effects of endogenously released histamine. 2. Guinea-pigs were actively sensitized to the specific antigen, ovalbumin. SCG removed from these animals rapidly released a significant proportion of their endogenous histamine stores into the extracellular space upon exposure to the sensitizing antigen. Several observations indicated that the released histamine was derived from ganglionic mast cells. 3. The electrophysiological effects produced by antigen challenge in a neurone mimicked qualitatively and quantitatively those effects produced by exogenously applied histamine in the same neurone. Under current clamp the membrane effects of antigen and histamine included a transient depolarization, an increase in input resistance and transient blockade of a long-duration component of the spike after-hyperpolarization. In voltage clamp histamine and antigen produced an inward current and decreased membrane conductance. 4. Histamine H1, but not H2 or H3 receptor antagonists prevented the membrane depolarization to both histamine and antigen treatments. 5. These convergent biochemical, physiological and pharmacological data demonstrate that a sufficient quantity of endogenous histamine is released by an antigenic stimulus in SCG from sensitized guinea-pigs to affect specific electrophysiological characteristics of neurones. Histamine may thus be involved in mediating interactions between the mammalian immune system and the peripheral sympathetic nervous system.

Action Potentials↗