Release of substance P-like immunoreactivity from the vascularly perfused rat stomach

The release of gastric substance P-like immunoreactivity (SP-LI) has been studied in the vascularly perfused rat stomach. In the presence of 20 μM bacitracin and captopril, basal release of SP-LI was sustained throughout the experiments. Gastric SP-LI release was stimulated in a concentration-dependent manner by increasing the concentration of KCl in the perfusion medium. This stimulated release was reduced by the omission of Ca²⁺, indicating that a Ca²⁺-dependent mechanism was involved. Naloxone did not alter basal SP-LI secretion. [Met⁵]Enkephalin also had no significant effect on K⁺-stimulated secretion suggesting that enkephalinergic mechanisms are not involved. Gastric SP-LI release was also increased by capsaicin perfusion but this was not sustained. In conclusion, the present results provide the first evidence for the release of SP-LI into the rat stomach vasculature.     

Evidence for presynaptic inhibitory histamine (H2) receptors in the rat hindquarter vasculature

Histamine released within walls of resistance blood vessels is suggested to mediate an active portion of baroreceptor-mediated neurogenic vasodilatation in skeletal muscle vasculature. Studies were undertaken to examine the possibility that histamine-mediated active vasodilatation could be effected, in part, by an inhibitory presynaptic action of histamine on vascular sympathetic varicosities. All experiments were conducted in constant-flow autoperfused rat hindquarters in which vasoconstrictor responses were evoked by sympathetic chain (L2-4) stimulation at varying frequencies or intraarterial norepinephrine (0.5 microgram) administration. Intraarterial histamine infusion resulted in a significant inhibition of nerve-stimulated hindquarter vasoconstriction, with the greatest reduction (20%) occurring at the 82.5-ng/ml/min dose. The inhibitory effect of histamine was not stimulation frequency dependent, and occurred when the vasoconstrictor responses to intraarterial norepinephrine and dilator responses to intraarterial nitroglycerin (1 microgram) were unaltered by the histamine infusions. The H2 agonist impromidine produced a significant inhibition of nerve-stimulated hindquarter vasoconstrictor responses without altering perfusion pressure responsiveness to either intraarterial norepinephrine or nitroglycerin. The magnitude of this inhibition of nerve-stimulated vasoconstrictor response was equivalent to or greater than that produced by histamine. The alpha 2-agonist clonidine produced a significant inhibitory effect on neurogenic vasoconstrictor responses with a maximum of 54%. Cimetidine infusion (10 mg/kg i.a.) essentially abolished the inhibitory effect of histamine on nerve-stimulated hindquarter vasoconstriction. These results are consistent with the existence of inhibitory presynaptic histamine receptors on sympathetic varicosities in the hindquarter vascular bed. Furthermore, evidence supports these inhibitory receptors being of the H2 class and the possibility that histamine-mediated active vasodilatation in rat hindquarters involves inhibitory presynaptic histamine receptors.     

Release of [Leu5]enkephalin immunoreactivity from the isolated perfused rat stomach

The release of [Leu5]enkephalin immunoreactivity ([Leu5]enk-IR) from the isolated perfused rat stomach was demonstrated under basal conditions in the presence of peptidase inhibitors (0.1 microM thiorphan, 1 microM captopril and 2 microM bestatin). Depolarization with 50 mM KCl resulted in a four-fold increase in both [Leu5]enk-IR and gastrin (IR-gastrin) levels. Administration of the nicotinic agonist, 1,1-dimethyl-4-phenyl-piperazinium (DMPP) (10 microM) stimulated the release of [Leu5]enk-IR in a calcium-dependent manner. The muscarinic acetylcholine receptor agonist methacholine (10 microM) had no effect on [Leu5]enk-IR release.     

Histological changes and histamine release induced by dactimicin in isolated perfused rat kidney

The nephrotoxicity of aminoglycosides has been the object of numerous works of research showing that different molecules belonging to the same family of antibiotics can exert their toxic action in different ways. The aim of the present research was to evaluate the nephrotoxicity of dactimicin (DTC), a recently synthesized aminoglycoside antibiotic, as compared to gentamicin (GTM), amikacin (AMK) and fortimicin (FTM). The experimental model used was the isolated perfused rat kidney, and the parameters evaluated were histamine release and histological findings. The results showed that GTM was able to induce a significantly higher release of histamine than AMK, FTM, or DTC. AMK provoked a higher level of histamine release than FTM or DTC, although the differences between the three were not significant. Histological preparations obtained with GTM revealed large-scale lesions, which however were less detectable with AMK, and much less with DTC.     

Release of histamine by substance P

1. The basic peptide substance P causes histamine release from peritoneal mast cells of the rat in vitro whereas the closely related neutral peptides eledoisin and physalaemin do not. 2. Infusion of substance P (7.4 nmol min-1), but not of eledoisin (8.4 nmol min-1) or physalaemin (7.9 nmol min-1), into the rat hindquarter preparation caused a more than 4-fold increase of the histamine content in the venous outflow. The outflow of 5-HT remained unchanged under infusion of all three peptides. 3. No histamine depletion in the skin of the rat hind paw was observed following antidromic stimulation of the saphenous nerve or cutaneous application of mustard oil. Infusion of substance P (7.4 nmol min-1) caused a 47% depletion of histamine in the paw skin although only a small proportion of the infused substance P seemed to enter the tissue from the blood vessels. 4. The results further substantiate the view that substance P upon release from peripheral nerve endings induces release of histamine from cutaneous mast cells, a mechanism which contributes to neurogenic vasodilatation and plasma extravasation.     

α1-adrenoceptor blockade by α2-adrenoceptor agonists in the isolated perfused hindquarter of rats

In isolated hindquarters of rats, perfused with modified Tyrode solution, the highly selective α₁-adrenoceptor agonist methoxamine decreased flow dose-dependently. This effect was antagonized by the highly selective α₂-adrenoceptor agonists B-HT 920, B-HT 933 (azepexole) and clonidine (pA₂ values: 4.9, 3.2 and 6.2, respectively). The results indicate either common structural features or interactions between α₁- and α₂-adrenoceptors.     

Vascular responses of the isolated perfused stomach of rabbit and rat to histamine

Gastric vascular responses to histamine and its selective H1- and H2-agonists in vitro were investigated in the isolated vascular-perfused stomach of rabbit and rat. In the rabbit stomach under resting conditions bolus injection of histamine (5-80 nmol) caused a small increase in perfusion pressure (PP). However, during infusion of noradrenaline (1 microM), which elevated vascular tone, histamine (5-80 nmol) caused a dose-dependent biphasic vascular response, an initial increase followed by a fall in PP. Under similar conditions, the H1-agonist 2-pyridyl ethylamine, (2-PE; 50-400 nmol) elevated PP, whereas the H2-agonist dimaprit (80-640 nmol) reduced PP. The H1-antagonist mepyramine (0.25 microM) converted the biphasic response of histamine (5-50 nmol) to a monophasic vasodilation whereas the H2-receptor antagonist, cimetidine (1 microM) converted the biphasic response to a vasoconstriction. Similar responses were observed during conditions of elevated vascular tone induced by vasopressin or angiotensin II. In the rat stomach, histamine and both dimaprit and 2-PE reduced PP during conditions of elevated vascular tone. These findings support the presence of both H1- and H2 receptors in the gastric vasculature of both rat and rabbit; in both species, the H2-response is vasodilation whereas the nature of the H1-response is species dependent.     

可乐定对自家血灌流毁脑脊髓大鼠后肢血管平滑肌的作用

本实验观察了可乐定对自家血恒速灌流的毁脑脊髓大鼠(pithed rat)后肢血管平滑肌的作用和该处突融后膜两种α受体亚型的存在。可乐定引起灌流压(PP)升高,呈剂量依赖关系,但效能远比选择性α_1受体激动剂苯福林低。对预先用利血平处理的大鼠,可乐定的作用被显著增强。高度选择性的α_1受体阻断剂哌唑嗪0.3mg/kg iv可部分阻断可乐定100μg ia的作用,增加哌唑嗪的剂量并不能进一步增加对可乐定的阻断作用。对于哌唑嗪不能阻断的部分,α_1受体阻断剂育亨宾却能表现出十分明显的抑制作用。这些结果提示在大鼠后肢血管平滑肌突触后膜上存在有α_1和α_2肾上腺素受体,但α_1受体似乎占优势。     

The effect of in vivo hyperoxic exposure on the release of endogenous histamine from the rat isolated perfused lung

Female rats were exposed to either 1 atm air or 100% O2 for 12, 24, or 48 hr. The rats were killed, the lungs were removed, and an isolated perfused lung (IPL) system was prepared. The isolated lung preparation was perfused with a modified Krebs-Henseleit buffer in a recirculating system, and the effect of the O2 exposures on histamine release from the IPL was determined. The effect of these O2 exposures on malondialdehyde formation in the IPL also was examined. Maximal release of histamine occurred after 20 min of perfusion. A linear relationship was found between the maximal histamine concentration released into the perfusate and the length of time the rats were exposed to normobaric hyperoxia. Malondialdehyde in lung perfusate also increased in a linear manner with increasing O2 exposure time. Addition of the H1-receptor antagonist, d-chlorpheniramine, to the perfusate completely inhibited basal histamine release from the IPL of both air- and O2-exposed rats, while addition of the H2-receptor antagonist, metamide, potentiated the release process. There was no significant effect demonstrated when an equimolar concentration of atropine was added to the perfusate. Arterial plasma histamine from rats exposed to 100% O2 for 24 hr increased 40% when compared to air-exposed controls, while histamine release from the IPL increased 75%. In conclusion, exposure of rats to normobaric hyperoxia caused both histamine release and malondialdehyde formation. Histamine release probably occurred as a result of a free radical-induced peroxidation of the lipid membrane of histamine-containing mast cells. Release of histamine from the IPL may be an early biochemical marker of damage by O2.     

Release of prostaglandins from the rabbit perfused kidney: Effects of vasoconstrictors

1 The rat stomach strip was used to assay prostaglandin E(2)-like material released by a rabbit isolated kidney perfused with Krebs solution.2 Doses of noradrenaline and angiotensin II producing similar vasoconstrictor effects released equivalent amounts of prostaglandins from the kidney.3 8-Leu-angiotensin II, a specific inhibitor of the natural octapeptide, blocked the action of angiotensin II on perfusion pressure and the release of prostaglandins, while the action of noradrenaline on both parameters was unaffected.4 Indomethacin, a specific inhibitor of prostaglandin biosynthesis, blocked the effects of both vasoconstrictors on prostaglandin release while their action on perfusion pressure was significantly enhanced.5 In the kidney effluent, amounts of prostaglandin E(2)-like material increased linearly with the rise in perfusion pressure induced by increasing doses of angiotensin II. These results indicate that prostaglandin output from the isolated kidney follows the rise in perfusion pressure.     

Release of smooth muscle-contracting substances from isolated perfused lungs.

Infusion of tryptamine (1-4 mug/ml) through the pulmonary circulation of rat isolated lung perfused with Krebs solution caused release of a mixture of spasmogens contracting isolated smooth muscle preparations. One component of this mixture had biological activity comparable to E-type prostaglandins. Other components included a slow reacting substance comparable to SRS-A and a rabbit aorta-contracting substance comparable to RCS. Infusions of 5-hydroxytryptamine, acetylcholine and histamine (0.5-2 mug/ml) also caused release. Release induced by the tryptamines but not that by acetylcholine and histamine was prevented by methysergide whereas acetylcholine-induced release was prevented by hyoscine which did not affect tryptamine-induced release. The tryptamines and histamine released spasmogens from dog isolated lungs but only histamine was effective in guinea-pig lungs. We conclude that amine-induced release from isolated lungs is a fairly general phenomenon and that it may represent an endocrine function of lung.     

Anaphylatoxin-induced release of histamine from in vitro perfused guinea pig kidney

The effect of porcine C5a des Arg and C3a, given as a bolus injection, in the isolated constant flow pump-perfused guinea-pig kidney was investigated. Only C5a des Arg showed activity which was manifested by a dose-dependent increase in perfusion pressure (PP, due to vasoconstriction) and histamine release. Although histamine release was substantial, it alone could not account for the increase in PP. The two more likely causes are a direct vasoconstrictor effect and the release of other mediators.     

Release of tissue histamine by the babesicidal agents quinuronium and amicarbalide

Quinuronium sulphate liberated appreciable quantities of histamine from tissues of mice, rats and sheep. The signs of quinuronium poisoning in mice and rats were more severe than for compound 48/80. The animals acquired tolerance to the latter drug. Thus the toxicity of quinuronium probably depended on factors other than histamine release. Amicarbalide released amounts of histamine comparable with those liberated by quinuronium only in rat tissues.     

A perfused tail artery preparation from the rat

The isolated perfused tail artery of the rat responds by constriction to 1·0 ng (-)-noradrenaline, and would be suitable for the assay of sympathomimetic amines. Electrical stimulation of this preparation is shown to activate solely postganglionic adrenergic nerve terminals. Tachyphyllaxis to angiotensin, vasopressin and bradykinin preclude the use of this preparation for their assay.     

Inhibition of insulin secretion from the perfused pancreas of the rat by pizotifen.

1 In the perfused rat pancreas the effects of pizotifen on insulin release induced by 20 mM glucose were studied. 2 Pizotifen (10 and 100 muM) significantly reduced the insulin release during a 25 min perfusion period to 49% and 7% of the controls. 3 The same concentrations of the structurally related agents cyproheptadine, doxepin, and chlorpromazine produced a comparable inhibition.     

Can the epithelium affect allergen-evoked histamine release from the perfused guinea pig trachea?

The aim of this study was to investigate the influence of the epithelium on allergen-evoked histamine release. Isolated tracheal preparations from guinea-pigs, with the epithelium either left intact or removed, were used. The trachea was perfused and challenged with egg-albumin (EA) either extra- or intraluminally. Fractions of the perfusate were collected for analysis of the histamine and EA contents. When EA was added intraluminally and the epithelium was removed, a marked peak in histamine release could be detected. In the presence of intact epithelium there was no marked histamine peak. EA added extraluminally gave the same results but the histamine peak was less pronounced. The epithelium apparently acts as a barrier, the nature of which remains to be elucidated.