Search PubMed⌕ Search

Biomedical subjects

P Holzer

Publications and source records attributed to P Holzer.

At least 181 records · Page 10Linked to original sources
PubMed1984

Release of endogenous 5-hydroxytryptamine from the myenteric plexus of the guinea-pig isolated small intestine.

The presence of 5-hydroxytryptamine (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in, and the release of these substances from, the myenteric plexus-longitudinal muscle (MPLM) layer of the guinea-pig isolated small intestine were investigated. 5-HT and 5-HIAA were measured by high performance liquid chromatography and electrochemical detection. Freshly prepared MPLM contained measurable amounts of 5-HT and 5-HIAA. For the release experiments, the MPLM was incubated in a medium containing the 5-HT uptake inhibitor fluoxetine and the monoamine oxidase inhibitor nialamide; this led to a decrease in the 5-HIAA content of the MPLM whereas the 5-HT content remained unchanged. There was a spontaneous release of 5-HT and 5-HIAA from the MPLM. The release of 5-HT was so small that it was just detectable; it seemed equivalent to about 0.8% of the tissue stores released per min. Depolarization of the tissue by increasing the [K+] or by exposing it to veratridine enhanced the release of 5-HT in a Ca2+-dependent manner whereas the release of 5-HIAA was not increased. Tetrodotoxin inhibited the veratridine-evoked release of 5-HT but did not affect the K+-evoked release of 5-HT. The presence of 5-HT in myenteric neurones and the characteristics of the release of 5-HT from these neurones strongly support the hypothesis that 5-HT is an enteric neurotransmitter.

Animals↗
PubMed1984

Substance P can contract the longitudinal muscle of the guinea-pig small intestine by releasing intracellular calcium.

The contraction of the longitudinal muscle of the guinea-pig isolated ileum in response to substance P (SP) in high [K+] medium and in Ca2+-free solution which contained EGTA has been investigated in order to examine whether excitation-contraction coupling involves the release of Ca2+ from an intracellular store. In tissues contracted by K+, high concentrations of SP (greater than or equal to 0.1 microM) were still capable of causing a slight, transient contraction. Bathing the ileum in a Ca2+-free medium for 2.5 min greatly diminished the potency and efficacy of SP in contracting the longitudinal muscle but concentrations of 2.2-22 microM SP were still able to produce a response 30-40% of maximal. The responsiveness to SP was completely lost within 10 min of bathing in Ca2+-free medium but was partially restored by a brief exposure (0.5-2 min) to high concentrations of Ca2+ (9-72 mM). The restorative effect of Ca2+ depended on the concentration of Ca2+ and on the time for which the tissue was exposed to this Ca2+ concentration. The fact that high concentrations of SP were able to elicit a contraction in media containing high [K+] or no Ca2+, suggested that they may do so by releasing Ca2+ from an intracellular store which is not as sensitive to removal of extracellular Ca2+ or as easily accessible to EGTA as the extracellular space of the muscle. The location of this store is not known; it may be associated with the internal side of the cell membrane. There is apparently an overlap between the Ca2+ pool associated with the action of SP and the Ca2+ pools utilized by acetylcholine, histamine or tetraethylammonium, which accounts for the cross-desensitization observed between these agonists. It was not possible to determine whether autodesensitization to SP also results from depletion of an intracellular Ca2+ store.

Acetylcholine↗
PubMed1984

Release of dynorphin, somatostatin and substance P from the vascularly perfused small intestine of the guinea-pig during peristalsis.

The release of dynorphin-(1-17), somatostatin and substance P into the venous effluate of the isolated and vascularly perfused guinea-pig small intestine was measured during rest and peristaltic activity. The peptides were determined by specific radioimmunoassays. Increasing the intraluminal pressure by 5 mbar increased the release of dynorphin-(1-17), somatostatin and substance P. A substantial increase in the release of substance P was only seen in the presence of naloxone (1.5 microM) indicating an inhibitory influence of opioid peptide-containing neurones on the release of substance P. The pressure-induced release of substance P and dynorphin-(1-17) was completely prevented by tetrodotoxin (1.3 microM), which suggests a neural origin of these two peptides. The pressure-induced release of somatostatin was only partially inhibited by tetrodotoxin (1.3 microM) suggesting that somatostatin may also be released from non-neuronal sources, i.e. endocrine mucosal cells. Dimethylphenylpiperazinium (32 microM) increased the release of somatostatin and substance P and this effect was inhibited by tetrodotoxin (1.3 microM). Cholecystokinin-octapeptide (38 nM) induced a large increase in the release of somatostatin but only a minute increase in the release of substance P; these effects of cholecystokinin-octapeptide were not blocked by tetrodotoxin (1.3 microM). Noradrenaline (59 microM) inhibited the pressure-induced release of substance P but not that induced by dimethylphenylpiperazinium (32 microM). Neither the pressure-induced nor the dimethylphenylpiperazinium-evoked release of somatostatin was significantly diminished by noradrenaline. These results indicate that dynorphin-(1-17), somatostatin and substance P may be transmitters involved in the coordination of the peristaltic reflex. Part of the inhibitory effects of opioid peptides and noradrenaline on intestinal motility may be brought about by inhibition of the release of substance P.

Animals↗
PubMed1983

Sympathetic control of substance P releasing enteric neurones in the guinea pig ileum.

The contractile response of the isolated guinea-pig ileum to cholecystokinin octapeptide (CCK-8) that remained in the presence of atropine was greatly inhibited by the substance P antagonist D-Pro2,D-Trp7,9-substance P. This indicates that the atropine-resistant contraction to CCK-8 is mediated by the release of substance P from enteric neurones. Activation of alpha-adrenergic receptors by noradrenaline, clonidine or mesenteric sympathetic nerve stimulation inhibited the atropine-resistant contraction to CCK-8 but did not affect the contractile effect of substance P. It is concluded that alpha-adrenergic receptors exert an inhibitory influence on the release of substance P from enteric neurones.

Adrenergic alpha-Agonists↗
PubMed1983

[D-Met2, Pro5]enkephalinamide and dynorphin-(1-13) inhibit the cholinergic contraction induced in the guinea-pig ileum by substance P.

In the isolated guinea-pig ileum, the sustained phase of the longitudinal contractile response to substance P is, unlike the initial peak response, mediated by stimulation of cholinergic neurons. This cholinergically mediated response to substance P was inhibited by the specific substance P antagonist, [D-Pro2,D-Trp7,9]substance P, which suggests that substance P stimulates enteric cholinergic neurons through a specific site of action. [D-Met2,Pro5]enkephalinamide and dynorphin-(1-13) also decreased whereas naloxone increased the sustained response to substance P. The results indicate that the enteric cholinergic neurons, which are stimulated by substance P, are also under the control of enkephalin and/or dynorphin neurons.

Animals↗
PubMed1983

On the mechanism of contraction and desensitization induced by substance P in the intestinal muscle of the guinea-pig.

The contractile effect of substance P on the longitudinal muscle of the isolated guinea-pig small intestine and the desensitization of the muscle which occurs on prolonged exposure to the peptide have been investigated. All experiments were performed in the presence of atropine. The response to a substance P concentration which produced a nearly maximal effect was not sustained but faded rapidly. It was found that not elimination of substance P from the bath, but desensitization of the muscle to substance P was the main cause for the fading of contraction. Desensitization of the muscle to substance P only developed if the muscle was exposed to the peptide for a certain time. The degree of and the time needed for recovery from desensitization were directly related to concentration of substance P and contact time. Tetraethylammonium (3 mM), which reduces the membrane conductance for K+, enhanced the potency of substance P in contracting the muscle and reduced the fading of contraction. Noradrenaline (295 nM), which increases the K+ conductance, produced opposite effects. Lowering the extracellular Ca2+ concentration to one-tenth decreased the potency of substance P in contracting the muscle, accelerated the fading of contraction, and reduced the ability of the muscle to respond to a second addition of substance P after the response to the first addition had faded away. Concentrations of substance P (22 nM) and tetraethylammonium (30 mM), which produced nearly maximal contractions, slightly enhanced the efflux of 86Rb from pre-loaded muscle strips. Both substances, however, caused a sustained reduction of 86Rb efflux from strips depolarized by high [K+], the effect of substance P being smaller than that of tetraethylammonium. The effect of substance P and tetraethylammonium on 86Rb efflux appeared independent of the extracellular [Ca2+]. On exposure of the muscle to substance P (22 nM) for 8 min the intracellular uptake of 45Ca was first decreased and then increased while the 45Ca influx was instantly enhanced by tetraethylammonium (30 mM) or K+ (108 mM). The delayed increase in 45Ca influx caused by substance P was also observed in muscle strips depolarized with high [K+].(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1982

Evidence for the involvement of substance P in the atropine-resistant peristalsis of the guinea-pig ileum.

In the isolated, vascularly perfused guinea-pig ileum, peristalsis could be induced by raising the intraluminal pressure in the presence of atropine. Atropine-resistant peristalsis was greatly inhibited or abolished by the substance P antagonist (D-Pro2, D-Trp7.9)-substance P, substance P desensitization, hexamethonium and by the enkephalin analogue FK 33-824. It is concluded that substance P neurones of the intestine play an important role in the atropine-resistant peristalsis of the guinea-pig ileum.

Animals↗
PubMed1982

Distribution of capsaicin-sensitive nerve fibres containing immunoreactive substance P in cutaneous and visceral tissues of the rat.

Treatment of newborn rats with capsaicin causes a selective and permanent degeneration of unmyelinated sensory fibres, some of which contain immunoreactive substance P (ISP). Following treatment of newborn rats with capsaicin (50 mg/kg), the ISP content was decreased by 66-75% in various skin areas and in the oral and nasal mucosae as measured at the age of 3-4 months. There was no significant depletion of ISP in the mucosa of the tongue. The ISP content of trachea, lungs, myocardium, hepatic duct, ureter and urinary bladder, was decreased by 60-84%. The ISP concentrations in stellate and mesenteric ganglia were reduced by 54 and 81%, respectively. These results indicate a widespread innervation of cutaneous and visceral tissues by sensory nerve fibers containing ISP.

Animals↗
PubMed1982

Different contractile effects of substance P on the intestine of mammals.

The contractile effect of substance P was examined on the longitudinal muscle of isolated sections of the gut of cat, guinea-pig, rabbit, and rat. Substance P caused contraction of all intestinal regions investigated, but there were marked qualitative and quantitative differences in the contractile responses to substance P. Low concentrations of substance P that did not cause tonic contraction (0.22--2.2 nM), increased the phasic longitudinal contractions observed in the ileum of cat, pig, and rabbit. Higher concentrations induced a tonic longitudinal contraction of the ileum, which in the cat, pig and rat was accompanied by facilitation and in the rabbit by inhibition of the phasic contractions. While in the ileum of guinea-pig and rabbit the maximal longitudinal contraction induced by substance P was equal to the maximal effect of acetylcholine, the maximal response to substance P was only about 50% of that to acetylcholine in the ileum of cat, pig, and rat. The jejunum, ileum and colon of the rabbit responded to substance P and acetylcholine was similar maximal contractions, but the jejunum appeared to be most and the ileum least sensitive to substance P. The results suggest qualitatively and quantitatively different roles of substance P in the intestinal motility of different mammals.

Animals↗
PubMed1982

A study of the concentrations of substance P and neurotensin in the gastrointestinal tract of various mammals.

Immunoreactive substance P and neurotensin in extracts of the digestive tract of man, cat, guinea-pig, pig, rabbit, and rat were measured by radioimmunoassay using antisera directed against the C-terminal portions of the two peptides. In all species except the cat, the concentrations of substance P were highest in the small intestine, intermediate in the large intestine and lowest in the stomach and oesophagus: the digestive tract of the cat displayed a rather even distribution of substance P. As observed in the ileum of guinea-pig, rabbit, and rat, the external muscle layer including the myenteric plexus contained 2-5 times higher concentrations of substance P than the whole ileal wall, whereas the substance P concentrations in the mucosa were only about one sixth of those in the whole wall. High performance liquid chromatography of extracts of human, feline and rabbit ileum showed that all the immunoreactive substance P eluted at the positions of substance P and substance P sulfoxide. The distribution of immunoreactive neurotensin along the digestive system of all six species was very similar. The highest concentrations of neurotensin were measured in the distal part of the small intestine, whereas the large intestine, stomach and oesophagus contained only low concentrations of neurotensin relative to the concentrations in the ileum. As examined in the ileum of guinea-pig, rabbit, and rat, the mucosa exhibited 2.5-4 times higher concentrations of neurotensin than the whole ileal wall, while the concentrations of neutrotensin in the external muscle layer including the myenteric plexus were only 4-20% of those in the whole wall. High performance liquid chromatography of the immunoreactive neurotensin extracted from the cat ileum yielded a single peak corresponding to neurotensin while the immunoreactive neurotensin extracted from the ileum of man and rabbit was eluted in two peaks, 55 and 72% of the recovered immunoreactivity, respectively, corresponding to neurotensin. These findings are in line with the proposed roles of substance P in the neural, and neurotensin in the endocrine, control and maintenance of gastrointestinal motility.

Animals↗
PubMed1982

An enquiry into the mechanism by which substance P facilitates the phasic longitudinal contractions of the rabbit ileum.

1. The effect of substance P on the phasic longitudinal contractions of the isolated rabbit ileum has been investigated. The contractions were recorded isotonically. Substance P in concentrations below those which cause tonic contraction (0.2-2 nM) increased the height of the phasic contractions in a concentration-dependent fashion without affecting their frequency (8-12/min).2. The effect of substance P was inhibited by verapamil, ouabain, noradrenaline, and isoprenaline, but was unaffected by tetrodotoxin, atropine, D-2-ala,5-metenkephalin, somatostatin, and vasoactive intestinal polypeptide.3. Tetraethylammonium, which blocks voltage-dependent K(+) channels, enhanced the phasic contractile activity of the rabbit ileum in a manner quite similar to substance P, but the maximal response to tetraethylammonium was larger than that to substance P.4. The effect of matched concentrations of substance P and tetraethylammonium, which enhanced the phasic contractions to a similar extent, was investigated at various concentrations of K(+), Na(+), Ca(2+) and Cl(-) in the bathing medium. Both substance P and tetraethylammonium lost their ability to enhance the phasic contractions when K(+) was omitted from the medium or when its concentration therein was increased by a factor of 4, or when the NaCl concentration was reduced to less than 10%. The relative increase in phasic contractile activity evoked by substance P was smaller than that evoked by tetraethylammonium when more than 90% of the Cl(-) was replaced with propionate.5. Noradrenaline, in a concentration which just abolished the spontaneous phasic contractions (200-300 nM), reduced the enhancing effect of substance P on the phasic activity by 40-50%, but did not influence the effect of tetraethylammonium.6. These results indicate that substance P enhances the phasic longitudinal contractions of the isolated rabbit ileum by a direct action on the smooth muscle cells and that this effect is brought about by facilitation of the myogenically controlled action potential discharges in the ileum. Circumstantial evidence suggests that the underlying ionic mechanism of action of substance P is a decrease in K(+) and Cl(-) conductances.

Animals↗
PubMed1982

Evidence that the contractile response of the guinea-pig ileum to capsaicin is due to release of substance P.

1. The possible roles of substance P and opioids in the contractile response of the isolated guinea-pig ileum to the sensory stimulant drug capsaicin were investigated, and the contractions were found to be inhibited by about 60% in preparations desensitized to substance P. 2. Contractions evoked by stimulation of the mesenteric nerves in the presence of the adrenergic blocking drug guanethidine were inhibited by about 75% after the ileum had been rendered insensitive to substance P. 3. Atropine partially inhibited the effect of capsaicin. The atropine-resistant component of the contractile response to capsaicin was inhibited by more than 85% in preparations desensitized to substance P and almost abolished by the substance P antagonist, (D-Pro2,D-Trp7,9)-substance P. 4. The opioid peptide (D-Met2, Pro5)-enkephalinamide inhibited, whereas the opiate antagonist naloxone enhanced the atropine-resistant contractions in response to capsaicin. 5. The results indicate that the contractile response of the guinea-pig ileum to capsaicin and mesenteric nerve stimulation is mediated by release of substance P, presumably from sensory nerve endings in the gut. Substance P appears to act on the smooth muscle both directly and indirectly via cholinergic neurones. It is proposed that opioids modulate the non-cholinergic response to capsaicin by inhibiting the release of substance P.

Animals↗
PubMed1982

In vitro release of endogenous catecholamines from the neural and intermediate lobe of the hypophysis.

This paper shows for the first time that the dopamine present in the neural and intermediate lobe (NIL) of the pituitary gland can be released in vitro by depolarization of the tissue with increased [K+]. The release is Ca++ dependent. This observation is in accordance with the concept that dopamine has a function as a neural transmitter substance in the NIL. At a [Ca++] of 2.5 mM it was also possible to measure the norepinephrine release from the NIL. The dopamine release from the NIL was unaffected by GABA. In contrast, the release of dopamine (but not of norepinephrine) from the medial-basal hypothalamus was enhanced by GABA.

Animals↗
PubMed1981

Histamine in tissue: determination by high-performance liquid chromatography after condensation with o-phthaldialdehyde.

Histamine was determined by reversed-phase high-performance liquid chromatography in perchloric acid extracts after condensation with o-phthaldialdehyde. Fluorescence was monitored at 360 nm excitation and 450 nm emission wavelengths after elution with mixtures of 0.1 N acetic acid containing 0.1% pentanesulfonic acid and acetonitrile. The detection limit was 0.9 pmol of histamine. The histamine content was determined in rat whole brain, medulla oblongata, dorsal and ventral spinal cord, dorsal and ventral skin of the hind paw, stomach, ileum, rectum, lung and a hind-quarter perfusate, and compared to published data. The advantages of the described method over other methods are (A) rapid analysis in an automated system, (B) no selective extraction procedure is necessary, and (C) interfering substances are easily separated from the histamine fluorophore.

Animals↗
PubMed1981

Substance P immunoreactive neurons following neonatal administration of capsaicin.

Neonatal administration of capsaicin on the days 2, 10 or 20 leads to a long-lasting loss of substance P immunoreactive material in fibers of primary sensory neurons in the spinal cord and medulla oblongata. The degree of depletion examined 6 months after treatment was related to the day of injection. Injections on the second day produced dramatic losses of substance P in fibers of the substantia gelatinosa and the marginal layer of the spinal cord and the spinal nucleus of the trigeminal nerve, although these losses were never complete. The observed depletion of substance P immunoreactive material was homogenous throughout the superficial layers of the dorsal horn and the spinal nucleus of the trigeminal nerve. No changes were observed for the immunoreactivity of Leu-enkephalin in the substantia gelatinosa and the marginal layer of the spinal cord in consecutive sections from the same treated animals. In the medulla oblongata a reduction of substance P immunofluorescent fibers was found in the nucleus tractus solitarii and the spinal nucleus of the trigeminal nerve. Other areas of the central nervous system with a rich innervation of substance P immunoreactive fibers were not affected by capsaicin treatment.

Animals↗