Search PubMed⌕ Search

Biomedical subjects

F Lembeck

Publications and source records attributed to F Lembeck.

At least 37 records · Page 2Linked to original sources
PubMed1992

Lack of significant unspecific effects of HOE 140 and other novel bradykinin antagonists in vitro and in vivo.

The novel, potent and long-acting bradykinin (BK) antagonists, HOE 140, compound II and compound III, slightly decreased blood pressure, but did not affect heart rate and respiration of rats. The antagonists did not cause bronchoconstriction in guinea-pigs. Neither HOE 140 nor BK released histamine from isolated perfused hindlegs of rats. The lack of significant unspecific side effects of the novel antagonists of effective doses will further increase the usefulness of these compounds for experimental and therapeutic purposes.

Animals↗
PubMed1992

[Pain and stress: biological protection].

The biological methods of animal organism protection, the role of stress and the nociceptive signals, the hierarchy of defence mechanism--from the autonomic reflexes, neuroendocrine regulations, emotional reactions and expressions up to peculiar to the human being intellectual safeguard have been considered. The latest data on the role of tachykinins in transmission have been examined. The discovery of mediator function of "substance P" (SP), other related peptides, which coexists and realizes from the primary afferents and other terminals of SP-containing, capsaicin-sensitive neurons--opened a new chapter in the neurobiology and medicine. The necessity to support the medico-biological (fundamental) experiments by the modern society is grounded.

Adrenal Glands↗
PubMed1991

Enzymic oxidation of capsaicin.

The oxidation of capsaicin (8-methyl-N-vanillyl-6-nonenamide) has been investigated by means of electrochemical, enzymic and chemical procedures. Capsaicin appears to form a fluorescent dimer comparable with those known to be formed from some other compounds bearing the vanillyl(4-hydroxy-3-methoxybenzyl-) group. If such a dimer of capsaicin were to be formed in tissues, it would bind tightly to lipid structures and its formation would prove difficult to follow. Tests on other substances bearing the vanillyl group that might be used to investigate the dimerization reaction in tissues and tissue extracts showed that 4-hydroxy-3-methoxyphenylacetic acid is a poor second substrate for peroxidase reactions. It was found that 2-methoxy-4-methylphenol (creosol) was more suitable. These results support the suggestion that the oxidation of capsaicin may be involved in some of its biological actions.

Capsaicin↗
PubMed1991

Neurogenic and non-neurogenic inflammation in the rat paw following chemical sympathectomy.

Rats with chemical sympathectomy, induced either at neonatal age (long-term sympathectomy) or in adult animals (short-term sympathectomy) by guanethidine or by 6-hydroxydopamine, were used to determine the contribution of sympathetic noradrenergic fibres to afferent neuron-mediated responses and to non-neurogenic inflammation in the rat. Following long-term sympathectomy with 6-hydroxydopamine there was a 66% depletion of noradrenaline in the paw skin. This was accompanied by a 20-53% increase in the levels of sensory neuropeptides in the paw skin and sciatic nerve. A hypersensitivity towards heat stimuli was observed in the tail immersion test. Neither neurogenic plasma protein extravasation following antidromic nerve stimulation or upon local mustard oil application nor the development of the non-neurogenic carrageenan oedema and its susceptibility towards indomethacin were impaired. Neonatal guanethidine sympathectomy caused an 86% depletion of noradrenaline in the paw skin and neurogenic plasma protein extravasation upon antidromic nerve stimulation was impaired. Sensory neuropeptides were unchanged in the skin after neonatal guanethidine and only calcitonin gene-related peptide content was increased in the spinal cord and sciatic nerves. The other observations (i.e. the sensitivity towards heat stimuli, the neurogenic mustard oil inflammation and the non-neurogenic carrageenan oedema) were similar to those observed after neonatal 6-hydroxydopamine treatment. Following the short-term treatment protocol of 6-hydroxydopamine, an 82% depletion of noradrenaline in the skin was accompanied by an increase in calcitonin gene-related peptide content, whereas after adult guanethidine (60% depletion of noradrenaline) levels of sensory neuropeptides were unchanged. Neurogenic plasma protein extravasation was found to be unimpaired after either type of short-term chemical sympathectomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗
PubMed1991

New, long-acting, potent bradykinin antagonists.

1. Three new bradykinin (BK) antagonists, D-Arg0-Hyp3-Thi5-D-Tic7-Oic8-BK (compound I), D-Arg0-Hyp3-D-Tic7-Oic8-BK (compound II), and Arg(Tos)1-Hyp3-Thi5-D-Tic7-Oic8-BK (compound III), were tested against the effects of BK in 9 bioassay preparations including visceral smooth muscles, vasoconstriction, plasma protein extravasation, release of prostaglandin E2, bronchoconstriction, and stimulation of afferent C-fibre nociceptors. In some of these tests the effects of the new compounds were compared with those of the antagonist D-Arg0-Hyp2-Thi5,8-D-Phe7-BK (compound IV), described by Stewart & Vavrek (1987). 2. For all bioassays the general rank order of potency of the compounds was found to be I greater than II greater than III much greater than IV. The new antagonists were long-acting; in some bioassays their effects outlasted the duration of the experiment. 3. The inhibitory effects of the new BK antagonists were specific for BK; actions of noradrenaline, angiotensin II, acetylcholine or histamine were unaffected by the antagonists. They did not stimulate the release of histamine or prostaglandins. An agonistic effect was observed only with very high concentrations of compounds I and II in the plasma protein extravasation test. 4. The long duration of action of the new BK antagonists is probably due to a high and long-lasting affinity to the BK receptors. A high resistance of the antagonists to enzymatic destruction may be another reason. 5. The new BK antagonists will be valuable tools for the investigation of the pathophysiological role of BK. In addition they may offer a potential for therapeutic applications.

Afferent Pathways↗
PubMed1990

Capsaicin desensitization in vivo is inhibited by ruthenium red.

The effect of systemic administration of Ruthenium Red on the excitatory and desensitizing effect of capsaicin was investigated in rats. Ruthenium Red was injected s.c. 30 min before capsaicin was administered. The excitatory effect of capsaicin on corneal, perivascular and visceral afferents was not influenced by treatment with Ruthenium Red. However, determination of the neuropeptide content and evoked neuropeptide release in peripheral organs and dorsal spinal cord 48 h after treatment showed that Ruthenium Red attenuated the 'desensitizing' effect of capsaicin at peripheral, but not at central, endings of primary afferents. On the other hand, a capsaicin-elicited autonomic reflex mediated by visceral afferents was still obtained in 9 of 14 rats that had received Ruthenium Red and capsaicin. The results indicate that a single dose of Ruthenium Red, which does not reduce the acute excitatory effect of capsaicin, reduces the desensitizing effect of capsaicin on peripheral endings of primary afferents in vivo. This long-lasting protective effect of Ruthenium Red suggests that it is possible to pharmacologically differentiate between the acute and chronic effects of capsaicin.

Animals↗
PubMed1990

Region-specific noradrenaline depletion by neonatal DSP-4: functional consequences and effect on a coexisting neurotransmitter.

Noradrenaline (NA) depletion following neonatal treatment of rats with DSP-4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzyl-amine) was not accompanied by any changes in neuropeptide tyrosine (NPY) levels. After 85-95% NA depletion in the spinal cord of DSP-4-treated rats, the reaction time in the tail withdrawal test was shorter than in the controls but the endogenous activation of the sympathetic nervous system in the baroreceptor reflex remained unchanged. These results suggest that the NA neurons in the spinal cord have an inhibitory function the processing of incoming sensory information.

Animals↗
PubMed1990

Absorption and metabolism of capsaicinoids following intragastric administration in rats.

This study was performed to examine the metabolism and absorption of intragastrically administered capsaicinoids in the anaesthetized rat. [3H]-dihydrocapsaicin ([3H]-DHC) and unlabelled capsaicin were readily absorbed from the gastrointestinal tract but were almost completely metabolized before reaching the general circulation. A certain degree of biotransformation already took place in the intestinal lumen. Unchanged compounds (identified by chromatography) were present in portal vein blood. There seems to be a saturable absorption and degradation process in the gastrointestinal tract and a very effective metabolism in the liver. Less than 5% of the total amount of extracted radio-activity consisted of unchanged [3H]-DHC in trunk blood and brain 15 min after gastrointestinal application. On the other hand, approximately 50% unchanged [3H]-DHC was detected in these tissues 3 min after i.v. or 90 min after s.c. application of the capsaicinoids. Dihydrocapsaicin (DHC) or [3H]-DHC were metabolized when incubated in vitro with liver tissue but not with brain tissue. The metabolic product(s) did not show capsaicin-like biological activity. It can be concluded that rapid hepatic metabolization limits systemic pharmacological effects of enterally absorbed capsaicin.

Animals↗
PubMed1990

Effects of carbonyl cyanide p-trichloromethoxyphenylhydrazone (CCCP) and of ruthenium red (RR) on capsaicin-evoked neuropeptide release from peripheral terminals of primary afferent neurones.

In the superfused isolated rat urinary bladder, capsaicin as well as electrical field stimulation evoked the release of calcitonin gene-related peptide-like immunoreactivity (CGRP-IR). Carbonyl cyanide p-trichloromethoxyphenylhydrazone (CCCP, threshold 2 microM) reduced both, the capsaicin- and the electrical field stimulation-evoked release of CGRP-IR while a low concentration of Ruthenium Red (RR, 0.6 microM and 2 microM) selectively attenuated the capsaicin-evoked release of CGRP-IR but did not influence the effect of electrical field stimulation. 20 microM RR nearly abolished the capsaicin-evoked release, but also attenuated the effect of electrical field stimulation. In the isolated guinea-pig bronchus, electrical field stimulation and capsaicin induced non-cholinergic contractions which are known to be caused by tachykinin release from afferent nerve terminals. CCCP (0.6 microM) only reduced the response to field stimulation; a ten-fold higher concentration of CCCP attenuated field stimulation as well as capsaicin-induced contractions. This is in contrast to the reported selective inhibition of capsaicin-induced contractions by RR. The present data demonstrate that CCCP generally inhibits evoked neuropeptide release, regardless of the kind of stimulation used while low concentrations of RR preferentially inhibit capsaicin-evoked neuropeptide release.

Animals↗
PubMed1990

Demonstration of extrapulmonary activity of angiotensin converting enzyme in intact tissue preparations.

1. The activity of angiotensin converting enzyme (ACE) has been studied on functional parameters of intact isolated preparations of extrapulmonary tissues. The conversion of angiotensin I (A I) to angiotensin II (A II) and the cleavage of bradykinin (BK) were used as indicators of ACE activity. Captopril was employed as a specific inhibitor of ACE. 2. Captopril augmented the BK-induced contractions of the rat isolated uterus, the BK- and substance P-induced contractions of the guinea-pig ileum, and the BK-induced venoconstriction in the isolated perfused ear of the rabbit. Degradation of BK by ACE was calculated to be 52% in the rat uterus and 75% in the rabbit perfused ear. 3. Captopril inhibited the A I-induced contractions of the rat isolated colon, the A I-induced vasoconstriction in the isolated perfused ear of the rabbit and the rise in blood pressure induced by i.a. injections of A I in pithed rats. Conversion of A I to A II was calculated to be 13% in the rat colon and 26% in the rabbit perfused ear. 4. From estimations of the A II activity (bioassay on the rat colon) in the effluent of the perfused ear of the rabbit after injections of A I into the arterial inflow cannula it was calculated that approximately one tenth of A I was converted to A II during a single passage through the ear (less than 15 s). 5. The present experiments suggest that the high activity of ACE in endothelium of blood vessels of extrapulmonary tissues may provide an additional (endothelium-dependent) local vasoconstrictor mechanism by the rapid formation of A II and inactivation of BK. The ACE activity in non-vascular smooth muscles, other than those of blood vessels, may also affect the physiological functions of these tissues.

Angiotensin II↗
PubMed1990

Different control of the adrenocorticotropin-corticosterone response and of prolactin secretion during cold stress, anesthesia, surgery, and nicotine injection in the rat: involvement of capsaicin-sensitive sensory neurons.

The release of ACTH, corticosterone, and PRL was compared in capsaicin-pretreated rats, which lack afferent C-fibers, and their controls under somatosensory (cold, surgery) and central (restraint) forms of stress. Cold stress induced the release of ACTH and consequently that of corticosterone in the controls, but not in the capsaicin-pretreated rats. Intravenous injection of ACTH1-24 was equally effective in releasing corticosterone in both groups. Whereas PRL was not released in response to cold stress, restraint stress did induce the release of both ACTH and PRL, in the capsaicin-pretreated as well as in the control group. Pentobarbital anesthesia alone elicited PRL, but no ACTH release. ACTH release was evoked by surgery under pentobarbital anesthesia but was abolished by capsaicin pretreatment. PRL levels were not further increased by surgery. Nicotine in a small dose (5 micrograms intra-arterially) evoked stimulation of afferent C-fibers as observed on a depressor reflex. Intraperitoneal injection of nicotine (250 micrograms/kg) caused a marked rise in plasma ACTH both in the capsaicin-pretreated conscious rats and in their controls, probably resulting from central stimulation as this effect was shown to be inhibited during pentobarbital anesthesia. A moderate rise of PRL by nicotine was seen in conscious rats. The stimuli used, regarded as experimental models of stress, show essential differences in their ability to evoke the release of ACTH, corticosterone, and PRL. Those stimuli which cause the release of ACTH and corticosterone via afferent C-fiber stimulation do not release PRL, whereas emotional and cognitive stress causes the release of both ACTH and PRL.

Adrenocorticotropic Hormone↗
PubMed1990

Functional analysis of kinin antagonists.

Peptide analogs of bradykinin (BK) containing unusual amino acids are potent antagonists of the actions of BK in various smooth muscle preparations. Apparent pA2 values above 7.0 could be demonstrated for Lys-Lys-[Hyp3, Thi5.8, D-Phe7]-BK (B4310) in the rat uterus and the rat duodenum. Actions of BK that are related to its possible role in inflammation could be antagonized in a specific and dose-dependent manner by B4310. Stimulation by BK of C fiber afferent neurons was investigated in the rabbit ear reflex preparation and in the isolated rabbit iris sphincter muscle. In both preparations, B4310 caused a parallel shift of the dose-response curves to BK. In the latter case, a pA2 value was established that agrees well with the values found on smooth muscles. However, the short duration of action of the antagonists suggested a rapid inactivation by peptidases.

Animals↗
PubMed1989

Ruthenium red selectively inhibits capsaicin-induced release of calcitonin gene-related peptide from the isolated perfused guinea pig lung.

In the present study the influence of Ruthenium red on capsaicin- and bradykinin-evoked neuropeptide release from primary afferent neurons was investigated in the guinea pig. Perfusion of the isolated guinea pig lung in vitro with a capsaicin (1 microM)-containing physiological salt solution increased the amount of calcitonin gene-related peptide-like immunoreactivity (CGRP-IR) in the outflow more than 20-fold. Ruthenium red (RR: 1 microM, 10 microM) dose-dependently reduced capsaicin-induced release of CGRP-IR. Addition of bradykinin (1 microM) to the perfusate induced a 3-fold increase of CGRP-IR in the outflow, which was not significantly reduced by 10 microM RR. These results suggest that RR represents a rather specific antagonist of capsaicin's action on sensory neurons.

Animals↗
PubMed1989

Effect of capsaicin on gastric corpus smooth muscle of the rat in vitro.

Circular strips of the rat gastric corpus muscle were mounted in Krebs solution for isometric tension recording. Addition of capsaicin usually led to either relaxation or contraction, but in some strips a biphasic response was observed. Although no clear-cut concentration-response relationship could be established, capsaicin predominantly induced contraction at 500 nM, whereas at 5 microM it mainly induced relaxation. In Krebs solution containing atropine plus guanethidine, the contraction induced by 500 nM capsaicin was significantly reduced. The contraction induced by capsaicin was abolished by spantide, a tachykinin antagonist, or by tachyphylaxis to substance P. Calcitonin gene-related peptide relaxed gastric smooth muscle, however, a dose-response relationship could not be established. This peptide contracted the muscle strips only at 1 microM. Tachyphylaxis to calcitonin gene-related peptide did not significantly influence the action of capsaicin. Vasoactive intestinal polypeptide dose dependently relaxed gastric corpus strips; however, these responses were qualitatively different from those to capsaicin. It is concluded that capsaicin contracts rat gastric smooth muscle via the release of tachykinins; cholinergic interneurones are involved. The mediator of the capsaicin-induced relaxation has yet to be determined.

Animals↗
PubMed1989

Ruthenium red selectively prevents capsaicin-induced nociceptor stimulation.

The effect of Ruthenium Red on capsaicin-induced stimulation of polymodal nociceptors was investigated in the isolated perfused rabbit ear with an intact neuronal connection. Ruthenium Red, 20 microM, completely prevented the response to capsaicin but not that to acetylcholine or bradykinin. It is therefore suggested that capsaicin activates sensory nerve terminals by a mechanism which is different from that for bradykinin or acetylcholine, and which can be blocked selectively by Ruthenium Red.

Acetylcholine↗