bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of 5‐HT3 receptors of N1E‐115 neuroblastoma cells by use of the influx of the organic cation [14C]‐guanidinium
Authors: Bönisch H. , Barann M. , Graupner J. , Göthert M. 
Published: July 2012

The 5‐HT3 receptor‐mediated cation influx into N1E‐115 mouse neuroblastoma cells has been studied by the use of the organic cation [14C]‐guanidinium.
5‐Hydroxytryptamine (5‐HT, 30 μm) caused a time‐dependent influx of [14C]‐guanidinium which, in contrast to the influx elicited by veratridine (100 μm), was not inhibited by tetrodotoxin (TTX, 10 μm). The 5‐HT‐induced influx was potentiated by substance P and inhibited by ondansetron.
5‐HT and the selective 5‐HT3 receptor agonists, m‐chloro‐phenylbiguanide, phenylbiguanide and 2‐methyl‐5‐HT caused bell‐shaped concentration‐response curves; the rank order of potency was m‐chlorophenylbiguanide > 5‐HT > phenylbiguanide = 2‐methyl‐5‐HT. Among these agonists, 5‐HT elicited the highest influx of [14C]‐guanidinium. 5‐Methoxytryptamine, an agonist at 5‐HT4 receptors, showed no effect.
The [14C]‐guanidinium influx induced by 100 μm 5‐HT was not affected by methysergide (10 μm) and ketanserin (10 μm) but was inhibited by 5‐HT3 receptor antagonists with the following rank order of potency: ICS 205–930 > ondansetron > MDL 72222 ≫ metoclopramide.
The 5‐HT‐induced [14C]‐guanidinium influx was increased in the absence of Ca2+ and/or Na+ and by a reduction of the temperature from 36° to 20°C.
Preincubation with 5‐HT (100 μm) caused a time‐dependent and rapidly reversible decrease of the 5‐HT‐induced [14C]‐guanidinium influx.
It is concluded that [14C]‐guanidinium influx measurement in N1E‐115 cells is a convenient method to study properties of the cation channel of the 5‐HT3 receptor. This influx is independent of the fast sodium channel.
Activation of ion channels by lysylbradykinin in the HCA‐7 colony 29 human adenocarcinoma cell line
Authors: Henderson R.M. , Cuthbert A.W. 
Published: July 2012

The patch‐clamp technique, both cell attached and inside‐out patches, was used to examine the effects of lysylbradykinin (LBK) and A23187 on ion channels in cultured Colony 29 epithelial cells derived from a human adenocarcinoma.
LBK and A23187 applied directly to the intact cell stimulated the opening of a number of types of ion channel including Ca2+‐activated K+ channels.
By use of inside‐out patches, anion channels could be stimulated to open by application of protein kinase A and ATP to the cytosolic surface. Ca2+‐activated K+ channels were also identified in isolated membrane patches.
The results suggest that the anion secretion which is stimulated by LBK is a complex event, involving the activation of a number of different types of ion channel, and that part of the response is the result of hyperpolarization of the cell by activation of Ca2+‐activated K+ channels. From the data presented in this and the accompanying papers it appears that the Ca2+‐sensitive K+ channels would be equally effective in either the apical or basolateral membranes.
Evidence against vasoactive intestinal polypeptide as the relaxant neurotransmitter in human cavernosal smooth muscle
Authors: Pickard R.S. , Powell P.H. , Zar M.A. 
Published: July 2012

The putative role of vasoactive intestinal polypeptide (VIP) as the relaxant neurotransmitter in human cavernosal smooth muscle has been studied in isolated tissue preparations.
Consistent neurogenic relaxations were evoked by electrical field stimulation (EFS; 2–64 pulses/train, 0.8 ms pulse duration, 10 Hz). VIP (0.1–3 μm) relaxed cavernosal smooth muscle in a dose‐dependent fashion. Relaxant responses to both EFS and VIP were reduced in tissue from impotent men.
Neurogenic relaxant responses were not diminished in the presence of the VIP‐inactivating peptidase, α‐chymotrypsin (α‐CT, 2 units ml−1). In contrast VIP‐induced relaxations were completely abolished.
Inhibition of nitric oxide synthase by NG‐nitro‐l‐arginine (30 μm), and of guanylate cyclase by methylene blue (50 μm) caused highly significant reductions of neurogenic relaxant responses whereas VIP‐evoked relaxations were unaffected.
It is concluded that VIP‐evoked relaxations are not mediated by the NO‐guanosine 3′:5′‐cyclic monophosphate (cyclic GMP) pathway and that VIP release is not essential for neurogenic relaxation of human cavernosal smooth muscle. VIP does not therefore act as the major relaxant neurotransmitter in this tissue.
Modulation of central noradrenergic function by RS‐15385‐197
Authors: Redfern W.S. , MacKinnon A.C. , Brown C.M. , Martin A.B. , Kilpatrick A.T. , Clague R.U. , Spedding M. 
Published: July 2012

RS‐15385‐197, a highly potent and selective α2‐adrenoceptor antagonist, was examined in a variety of in vitro and in vivo functional tests to assess the selectivity of its interaction with central noradrenergic neurones in the rat.
In hypothalamic slices, RS‐15385‐197 was potent in augmenting K+‐evoked release of [3H]‐noradrenaline, with an EC50 of 9 nm. Idazoxan and yohimbine showed 100 fold less activity. This was due to its antagonist action at presynaptic α2‐adrenoceptors, as RS‐15385‐197 (10 μm), did not directly release [3H]‐noradrenaline from cortical slices unlike reserpine (10 μm), and did not inhibit noradrenaline re‐uptake into cortical synaptosomes.
In vivo, RS‐15385‐197 (0.5 mg kg−1, p.o.) increased levels of 3‐methoxy‐4‐hydroxy‐phenylglycol (MHPG) in the cerebral cortex without modifying levels of 5‐hydroxyindoleacetic acid (5‐HIAA). This dose, but not a lower dose (0.1 mg kg−1, p.o.) caused β‐adrenoceptor down‐regulation in the cortex when administered once daily for 14 days whereas 5‐HT2 receptor number was unaltered, indicating a selective effect on noradrenergic transmission.
Selective depletion of cortical 5‐HT by administration of p‐chlorophenylalanine (PCPA; 100 mg kg−1, i.p. for 14 days) or 5,7‐dihydroxytryptamine (5,7‐DHT; 150 μg i.c.v.) prevented the β‐adrenoceptor down‐regulation caused by RS‐15385‐197, indicating that a tonic 5‐hydroxytryptaminergic input was required for it to elicit β‐adrenoceptor down‐regulation. It was not possible to prevent the loss of activity of RS‐15385‐197 in these 5‐HT‐depleted animals by co‐administration with the 5‐HT1A partial agonist, 8‐hydroxy‐n‐dipropyl aminotetralin (8‐OH‐DPAT, 0.3 mg kg−1, i.p. twice daily for final 3 days).
At a dose (1 mg kg−1, p.o.) which completely prevented the hypoactivity produced by clonidine (0.1 mg kg−1, p.o.), RS‐15385‐197 did not affect behavioural stereotypy induced by 8‐OH‐DPAT (0.3 mg kg−1, s.c.). Similarly, following chronic dosing with the racemate, RS‐15385‐196 (3 mg kg−1, p.o., once daily for 14 days), there was no effect on the behavioural and hypothermic response to 8‐OH‐DPAT (0.5 mg kg−1, s.c.). Therefore, RS‐15385‐197 was selective for central α2‐adrenoceptors over 5‐HT1A receptors in in vivo functional tests.
Thus, RS‐15385‐197 was highly selective in interacting with central noradrenergic neurones in the rat in vitro and in vivo. It is therefore currently the agent of choice for investigations of the role of α2‐adrenoceptors in the CNS.
Endothelin (16–21): biphasic effect and no desensitization on the guinea‐pig isolated ileum
Authors: Miasiro N. , Nakaie C.R. , Paiva A.C.M. 
Published: July 2012

In the guinea‐pig ileum the C‐terminal hexapeptide of the endothelins, endothelin (16–21), induced a biphasic effect (relaxation followed by contraction) qualitatively similar to that seen in the responses to endothelins 1 and 3. Both components of the response were concentration‐dependent in the range studied (2–100 μm).
The response induced by endothelin (16–21) was inhibited in low‐sodium (80 mm) medium.
Repeated administration of endothelin (16–21) induced no desensitization of the preparation, contrasting with the tachyphylaxis induced by endothelin‐1 and endothelin‐3 in the guinea‐pig ileum.
Tissues rendered tachyphylatic to endothelin‐1 or endothelin‐3 responded normally to endothelin (16–21).
The results suggest that the C‐terminal tail of the endothelins contains the message for the biphasic response, whereas the N‐terminal domain may be responsible for the strong binding to the receptor and for the tachyphylactic properties of endothelin‐1 and endothelin‐3, in the guinea‐pig isolated ileum. However, the possibility that endothelin (16–21) may be acting on a site other than the endothelin receptor cannot be ruled out.
Calcium antagonistic and antiarrhythmic actions of CPU‐23, a substituted tetrahydroisoquinoline
Authors: Dong Hui , Sheng Jian‐Zhong , Lee Chi‐Ming , Wong Tak Ming 
Published: July 2012

The effects of CPU‐23 (1‐{1‐[(6‐methoxyl)‐naphth‐2‐yl]}‐propyl‐2‐(1‐piperidine)‐acetyl‐6,7‐dimethyoxy‐1,2,3,4‐tetra‐hydroisoquinoline) were studied on mechanical and electrical activities, and intracellular free calcium ([Ca2+]i) of isolated cardiac tissues in order to investigate its spectrum and mechanisms of action in the heart. Its antiarrhythmic and haemodynamic effects in pentobarbitone‐anaesthetized rats subjected to coronary artery ligation were also evaluated.
CPU‐23 at 10−6‐10−4 m markedly inhibited slow action potential characteristics in guinea‐pig papillary muscles and pace‐maker action potential of rabbit sinoatrial node. It affected fast action potential only at 10−4 M. None of the effects of CPU‐23 was reversed by washout for up to 2 h.
Like nifedipine and diltiazem, CPU‐23 decreased the heart rate of the isolated perfused heart of the rat. However, in contrast to these two classical calcium antagonists which dose‐dependently inhibited the force of contraction, CPU‐23 inhibited and stimulated the force of contraction at 10−7‐3 × 10−6 m and 10−5 m, respectively.
CPU‐23 at 10−6‐10−5 m inhibited the KCl‐induced [Ca2+]i increase in the Ca2+ medium, but did not affect the caffeine‐induced [Ca2+]i increase in the Ca2+‐free medium in isolated ventricular myocytes.
CPU‐23 at 1–5 mg kg−1 reduced dose‐dependently ventricular arrhythmias including ventricular ectopic beats, VT and VF as well as mortality during coronary artery ligation. At 2.5–5 mg kg−1 it even abolished VF, which was accompanied by 100% survival.
It is suggested that CPU‐23 has calcium antagonistic properties in cardiac tissues. It selectively blocks the transmembrane influx of extracellular Ca2+ through Ca2+ channels, thus reducing the heart rate and developed tension, altering the slow action potential characteristics and producing antiarrhythmic effect against ischaemic arrhythmias.
Whole cell and single channel analysis of the kinetics of glycine‐sensitive N‐methyl‐D‐aspartate receptor desensitization
Authors: Parsons Chris G. , Zong Xiangang , Lux Hans D. 
Published: July 2012

The kinetics of glycine‐sensitive, N‐methyl‐d‐aspartate (NMDA) receptor desensitization were investigated in cultured neurones with the patch clamp technique.
The degree of fast NMDA‐receptor desensitization was inversely related to glycine concentration. Thus, increasing concentrations of glycine from 30 nm to 2.5 μm potentiated desensitized NMDA responses (873% ± 101%) to a greater degree than peak responses (260% ± 27%).
The desensitization was due to a decrease in the affinity of glycine for the strychnine‐insensitive, glycine modulatory site (glycineB site) following activation of the NMDA‐receptor complex. Thus, the A50 for glycine in potentiating peak responses (77 nm, 95% confidence limited 58–104 nm) was five fold lower than that for plateau responses (399 nm, 340–468 nm).
The rate of desensitization was related to glycine concentration such that a reciprocal plot of desensitization rate (1/τ S−1) against glycine concentration had a slope of 9.5* 106 M−1 S−1.
Recovery from desensitization following step increases in glycine or l‐alanine concentration in the continuous presence of NMDA (200 μm) reflected the association kinetics of the glycineB agonist used.
The rate and degree of NMDA receptor desensitization was independent of holding potential.
NMDA receptor desensitization was also evident at the single channel level.
The glycineB antagonist 7‐chlorokynurenic acid (7‐Chl‐Kyn 3 and 10 μm) concentration‐dependently induced an identical form of desensitization in the presence of 1 μm glycine.
In contrast, the competitive NMDA antagonist (±)‐amino‐phosphonovaleric acid (APV 30 to 300 μm) concentration‐dependently antagonized and slowed the onset kinetics of NMDA responses.
Characterization of propranolol‐resistant (−)‐[125I]‐cyanopindolol binding sites in rat soleus muscle
Authors: Roberts Susan J. , Molenaar Peter , Summers Roger J. 
Published: July 2012

The characteristics of a propranolol‐resistant (−)‐[125I]‐cyanopindolol (CYP) binding site in rat soleus muscle were determined.
Saturation studies performed on homogenates of rat soleus muscle showed two phases of (−)‐[125I]‐CYP binding, a high affinity site (KD1 30.5 ± 16.3 pm, Bmax 9.4 ± 1.38 fmol mg−1 protein) and a lower affinity site (KD2 522.5 ± 29.1 pm, Bmax 62.19 ± 11.76 fmol mg−1 protein, n = 4).
In rat soleus muscle homogenates labelled with (−)‐[125I]‐CYP (500 pm), (−)‐propranolol competition curves were biphasic with pKD values of 8.30 ± 0.19, and 5.33 ± 0.08, n = 7.
Competition between (−)‐[125I]‐CYP (500 pm) and (±)‐tertatolol, (±)‐nadolol, (±)‐alprenolol, (±)‐CYP, and (−) and (+)‐pindolol showed that these compounds competed for binding at the propranolol‐resistant site with affinities lower than those displayed at typical β‐adrenoceptors. The atypical β‐adrenoceptor agonists BRL 37344, SR58611A and ICI D7114 and the partial agonist (±)‐CGP 12177 also competed for (−)‐[125I]‐CYP binding.
Stereoselectivity was demonstrated for the stereoisomers of alprenolol and tertatolol. The (−)‐isomers of alprenolol and tertatolol had higher affinity than their corresponding (+)‐isomers (3.1 and 2.6 fold respectively). These low stereoselectivity values are a characteristic of atypical β‐adrenoceptors.
The β‐adrenoceptor agonists, (−)‐adrenaline, (−)‐isoprenaline and (−)‐noradrenaline, all showed lower affinity than the atypical β‐adrenoceptor agonists and competition curves appeared biphasic in nature.
These results confirm the presence of a propranolol‐resistant (−)‐[125I]‐CYP binding site in rat soleus muscle. The affinities of the tested compounds at the propranolol‐resistant (−)‐[125I]‐CYP binding site show similarities to their affinities at ‘atypical’ β‐adrenoceptors in adipocytes and gastrointestinal tissues and at the cloned β3‐adrenoceptor.
Excitatory amino acid receptor‐stimulated phosphoinositide turnover in primary cerebrocortical cultures
Authors: Birrell Graham J. , Marcoux Frank W. 
Published: July 2012

Characterization of excitatory amino acid‐induced accumulation of [3H]‐phosphoinositides was carried out in primary cerebrocortical cultures isolated from foetal rats.
All of the excitatory amino acid receptor agonists examined caused concentration‐dependent enhancement of phosphoinositide (PI) formation. The most potent excitatory amino acid receptor agonists were quisqualate, (1S,3R)‐1‐aminocyclopentane‐1,3‐dicarboxylic acid ((1S,3R)‐ACPD), ibotenate and glutamate with mean EC50 values of 0.9 ± 0.4 μm, 15 ± 5 μm, 15 ± 3 μm and 41 ± 8 μm respectively.
The selective ionotropic receptor antagonists kynurenic acid (1 mm), 2,3‐dihydroxy‐6‐nitro‐7‐sulphamoyl‐benzo(F)quinoxaline (NBQX, 10 μm) and (±)‐4‐(3‐phosphonopropyl)‐2 piperazinecarboxylic acid (CPP, 100 μm), failed to block responses to quisqualate, (1S,3R)‐ACPD or glutamate. d,l‐2‐Amino‐3‐phosphonopropionate (d,l‐AP3) did not block 1S,3R‐ACPD or quisqualate‐induced PI turnover, but had an additive effect with quisqualate or (1S,3R)‐ACPD.
Exposure of cultures to agonists in the absence of added extracellular calcium reduced the maximal quisqualate response by approximately 45%, revealing a two‐component concentration‐response curve. Concentration‐response curves to ibotenate and glutamate became flattened by omission of extracellular calcium, whereas (1S,3R)‐ACPD‐stimulated PI turnover was unaffected.
Pretreatment of cultures with pertussis toxin markedly inhibited PI responses evoked by (1S,3R)‐ACPD.
These results suggest that excitatory amino acid‐stimulated PI turnover in cerebrocortical cultures is independent of ionotropic receptor activation and is mediated via specific G‐protein‐linked metabotropic receptors. The partial dependence of the responses to quisqualate, ibotenate and glutamate on the presence of extracellular calcium suggests that the effects of these agonists may be mediated by more than one receptor subtype.
Modulation of vasodilatation to levcromakalim by hypoxia and EDRF in the rabbit isolated ear: a comparison with pinacidil, sodium nitroprusside and verapamil
Authors: Randall Michael D. , Griffith Tudor M. 
Published: July 2012

We have used an isolated buffer‐perfused preparation of the rabbit ear to investigate the effects of hypoxia and inhibition of endothelium‐derived relaxing factor (EDRF) synthesis on the vasodilator responses to the potassium channel opener, levcromakalim (the active (−)‐enantiomer of cromakalim). The results obtained with levcromakalim have been compared with those for pinacidil, sodium nitroprusside and verapamil.
Levcromakalim relaxed preconstricted preparations with an EC50 = 343 ± 41 nm and Rmax = 80.3 ± 6.4%. Under hypoxic conditions the concentration‐response curve was significantly (P < 0.01) shifted to the left with an EC50= 118 ± 16 nm and Rmax = 89.9 ± 2.7%. Hypoxia did not influence relaxation to either pinacidil, sodium nitroprusside or verapamil.
Inhibition of EDRF synthesis with 100 μm NG‐nitro‐l‐arginine methyl ester (l‐NAME) also significantly (P < 0.001) increased the vasodilator potency of levcromakalim (EC50 = 56 ± 5 nm), and caused a similar shift in the concentration‐response curve to sodium nitroprusside. It did not influence vasodilatation to either verapamil or pinacidil. The potentiation of vasodilator responses to levcromakalim by l‐NAME was reversed by an excess of l‐arginine.
Impairment of oxidative phosphorylation with 400 nm carbonyl cyanide m‐chlorophenylhydrazone significantly (P < 0.05) increased the potency of levcromakalim (EC50 = 120 ± 20 nm) but did not influence vasodilatation to pinacidil or endothelium‐dependent relaxations to acetylcholine.
Vasodilatation to levcromakalim was augmented both by hypoxia and by inhibition of EDRF activity. Since impairment of oxidative phosphorylation increased the potency of levcromakalim but did not alter EDRF activity then the mechanism responsible for hypoxic facilitation of responses to levcromakalim is likely to be due to reduced ATP levels in hypoxic smooth muscle cells rather than a change in EDRF activity. These results suggest that levcromakalim may selectively dilate both hypoxic vessels and vessels with impaired EDRF activity. The results also point to important differences in the pharmacology of levcromakalim and pinacidil.
Selective MPP+ uptake into synaptic dopamine vesicles: possible involvement in MPTP neurotoxicity
Authors: Del Zompo M. , Piccardi M.P. , Ruiu S. , Quartu M. , Gessa G.L. , Vaccari A. 
Published: July 2012

In the present study we provide evidence for a saturable, Mg2+/ATP‐ and temperature‐dependent, tetrabenazine‐, dopamine‐, and amphetamine‐sensitive uptake of 1‐methyl‐4‐phenylpyridinium ion (MPP+) in synaptic vesicles from mouse striatum.
Similarity in the properties of the vesicular uptake suggests that in the striatum dopamine and MPP+ share the vesicular carrier.
The presence of MPP+ vesicular uptake in dopamine‐rich regions such as striatum, olfactory, tubercles and hypothalamus, as well as its absence in cerebellum, cortex and pons‐medulla, suggest that monoamine vesicular carriers differ between highly and poorly dopamine‐innervated regions.
The restriction of active MPP+ uptake to the dopaminergic regions, which reflects the previously shown distribution of [3H]‐MPP+ binding sites in mouse brain membranes, indicates MPP+ as a marker of the vesicular carrier for dopamine in dopaminergic neurones.
A role in MPP+ neurotoxicity is suggested for this region‐specific, vesicular storage of the toxin.
Changes in [3H]‐PK 11195 and [3H]‐8‐OH‐DPAT binding following forebrain ischaemia in the gerbil
Authors: Kenny B.A. , MacKinnon A.C. , Spedding Michael , Brown Christine M. 
Published: July 2012

A high density of [3H]‐PK 11195 binding sites was present in gerbil cortical membranes (Bmax [3H]‐PK 11195 1360 ± 71 fmol mg−1 protein) in comparison to rat cortical membranes (254 ± 21 fmol mg−1 protein). This effect was species‐specific as similar findings were obtained with hippocampal membranes (Bmax 1430 ± 111 fmol mg−1 protein in gerbil, compared to 196 ± 31 in rat).
RO 5–4864, also a peripheral type benzodiazepine compound, displayed low affinity for the [3H]‐PK 11195 site in the gerbil (pKi 6.57 ± 0.02 and 6.70 ± 0.12 in hippocampus and cortex respectively) compared to rat (pKi 8.16 ± 0.07 and 8.48 ± 0.02). Central benzodiazepine compounds, diazepam and flunitrazepam, also displayed this trend.
RO 5–4864 displaced [3H]‐PK 11195 binding from gerbil and rat cortical membranes through a competitive interaction with Hill slopes close to unity. In both tissues, saturation isotherms of [3H]‐PK 11195 binding indicated that the presence of RO 5–4864 caused changes in Kd without any effect on Bmax. In kinetic experiments, the presence of RO 5–4864 failed to modify the rate of dissociation of [3H]‐PK 11195 from equilibrium in both rat and gerbil cortical membranes.
Forebrain ischaemia in the Mongolian gerbil (5 min bilateral carotid artery occlusion) with 7 days recovery caused a significant (P < 0.05) decrease in the density of hippocampal 5‐HT1A binding sites labelled by [3H]‐8‐OH‐DPAT (Bmax control, 393 ± 33 fmol mg−1 protein; ischaemic, 289 ± 21 fmol mg−1 protein) and an increase (P < 0.01) in [3H]‐PK 11195 binding sites (Bmax control, 1430 ± 111 fmol mg−1 protein; ischaemic, 2160 ± 170 fmol mg−1 protein). Ischaemia and recovery had no effect on the affinity of either ligand.
Autoradiography experiments in gerbil brain sections revealed that the ischaemia‐induced increase in [3H]‐PK 11195 binding was consistent and significant in the CA1 subfield on the hippocampus (control, 152 ± 42 fmol mg−1 tissue; ischaemic; 314 ±; 43 fmol mg−1 tissue).
A comparison of the effects of polyarginine and stimulated eosinophils on the responsiveness of the bovine isovolumic bronchial segment preparation
Authors: Omari Taher , Sparrow Malcolm P. , Church Martin K. , Holgate Stephen T. , Robinson Clive 
Published: July 2012

The bovine isovolumic bronchial segment preparation has been used to study the sensitivity and responsiveness of bronchial smooth muscle after various manipulations.
Addition of acetylcholine (ACh) to the lumen of the segments elicited an increase in intraluminal pressure as a result of contraction of the airway smooth muscle. However, the increases in intraluminal pressure were greater when the ACh was added to the adventitial surface of the preparation.
Addition of polyarginine to the bronchial lumen for 60–120 min resulted in an increased magnitude of response and greater than 100 fold increase in sensitivity to ACh administered into the lumen. Depolarizations induced by KCl were similarly enhanced when the solution was added into the lumen. In contrast, the sensitivity and responsiveness to ACh or K+‐induced depolarization administered adventitially was unchanged.
The mechanical disruption of the epithelium produced a 32 fold increase in sensitivity to ACh introduced via the lumen, whereas the sensitivity to ACh added adventitially remained unaltered.
Addition of polyarginine to the adventitial bathing medium resulted in no change in the responsiveness or sensitivity to ACh, irrespective of whether the ACh was given intraluminally or adventitially.
Histological examination revealed that polyarginine caused extensive disordering of the normal architecture of the bronchial epithelium. Taken together with the unaltered responsiveness to adventitial ACh (i.e. lack of change in intrinsic muscle sensitivity) these observations suggest that the effect of polyarginine was most likely due to disruption of a diffusion barrier.
In contrast to the effects of polyarginine, the only effect of stimulated eosinophils was to produce a small diminution in the responsiveness to ACh that had been added adventitially.