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Biomedical subjects

R Gamse

Publications and source records attributed to R Gamse.

At least 37 records · Page 2Linked to original sources
PubMed1986

Nociceptive behavior after intrathecal injections of substance P, neurokinin A and calcitonin gene-related peptide in mice.

Intrathecal injections of substance P (SP) or neurokinin A (NKA) in the mouse caused dose-dependent reciprocal hindlimb scratching, licking and biting responses directed to the caudal part of the body. NKA decreased the latency in the tail flick assay but like SP, did not alter the reactions in the hot plate test or the hypertonic saline assay. Although immunoreactivity of calcitonin gene-related peptide (CGRP) was detected in mouse spinal cord, CGRP caused no behavioral reactions, nor did it significantly affect thermo- or chemonociception or the scratching induced by SP. Since NKA-like immunoreactivity was found to be present in sensory neurons, NKA as well as SP are likely transmitters of nociceptive primary afferent neurons.

Animals↗
PubMed1986

Behavioral and neurochemical changes after intracisternal capsaicin treatment of the guinea pig.

Guinea pigs were treated with 125-150 micrograms capsaicin intracisternally (i.c.) or intraperitoneally (i.p.). Tested up to one week later, i.c.-treated animals showed reduced behavioral responses to the irritating effects of capsaicin applied to the eye or nose, to ether vapor, cigarette smoke and to hot water (50 degrees C) applied to the forepaw or ear. The concentrations of substance P (SP)- and neurokinin-immunoreactivity were decreased in the medulla oblongata but not in the trigeminal root of i.c.-treated animals as compared to controls or i.p.-treated guinea pigs. These results suggest that i.c. capsaicin causes a degeneration of the central terminals of chemo- and thermonociceptive afferent neurons, some of which contain the putative neurotransmitters SP and neurokinin A.

Animals↗
PubMed1986

Simultaneous release of several tachykinins and calcitonin gene-related peptide from rat spinal cord slices.

Superfusion of slices of the dorsal half of rat spinal cord in vitro with 10 microM capsaicin or 60 mM potassium lead to the simultaneous release of substance P (SP)-, neurokinin A (NKA)- and calcitonin gene-related peptide (CGRP)-like immunoreactivities (LI). The ratio between capsaicin-stimulated and basal release was higher for CGRP-LI than for SP-LI, indicating that relatively more CGRP is released from sensory nerves, whereas SP is not only released from afferent neurons. High-performance liquid chromatography of NKA-LI revealed several immunoreactive components. One major peak had the retention time of synthetic NKA. A second peak eluted close to the position of synthetic eledoisin. In conclusion, capsaicin releases several bioactive peptides from sensory neurons which may mediate the acute algetic effect of chemical irritants.

Animals↗
PubMed1986

Bronchial, cardiovascular and secretory responses after central administration of capsaicin in the guinea-pig.

Capsaicin was injected intracisternally (i.c.), intrathecally (i.th.) or intravenously (i.v.) into guinea-pigs anaesthetized with urethane and ventilated artificially. The effects of 0.2-100 micrograms capsaicin on insufflation pressure, heart rate, arterial blood pressure and salivation were recorded. Low i.c. doses of 0.2 and 2 micrograms capsaicin induced bradycardia, hypertension and salivation but no change in insufflation pressure. An insufflation pressure increase, i.e. bronchoconstriction, was observed with 20 or 100 micrograms capsaicin i.c. and this was associated with tachycardia and hypertension. Bronchoconstriction after 20 micrograms capsaicin i.c. was augmented by propranolol (1 mg/kg i.v.). It was, however, unaffected by bilateral cervical vagotomy and could also be induced by i.th. capsaicin injections in the lumbar region. Capsaicin (3 micrograms/kg) injected i.v. induced bronchoconstriction and tachycardia. Propranolol enhanced bronchoconstriction but did not reduce the tachycardia indicating that capsaicin led to activation of sympathetic bronchial but not cardiac fibers. These results also indicate that i.c. capsaicin caused reflex responses consisting of salivation, bronchodilatation bradycardia and hypertension. High doses injected i.c. or i.th. also caused tachycardia and bronchoconstriction. This latter effect, however, was neither a vagal reflex nor did it seem to result from activation of central terminals of afferent fibers with subsequent release of mediators from the peripheral endings due to antidromic spread of nerve impulses. Instead, capsaicin seemed to be readily resorbed into the systemic circulation and thus acting at peripheral endings to cause bronchoconstriction and tachycardia.

Airway Resistance↗
PubMed1986

Capsaicin induced release of multiple tachykinins (substance P, neurokinin A and eledoisin-like material) from guinea-pig spinal cord and ureter.

The release of tachykinins from isolated slice preparations of the guinea-pig spinal cord and ureter was studied in vitro. Capsaicin (10 microM) caused release of substance P, neurokinin A and an eledoisin-like component from both the spinal cord and ureter. The release of tachykinins induced by capsaicin or potassium (60 mM) was calcium dependent. No detectable release of neurokinin B or neuropeptide K, an N-terminally extended form of neurokinin A, was induced by capsaicin. No detectable release of tachykinins could be demonstrated after exposure to agents which are known to activate C-fibre afferents, such as histamine, bradykinin, serotonin, prostaglandins E1, E2 or acetylcholine. Protein extravasation in the ureter, as determined by the Evans Blue extravasation technique was used as a functional correlate to the tachykinin release. Protein extravasation was induced in vivo by local intraluminal injections of capsaicin at several hundred-fold lower concentrations than those required to induce a detectable release of tachykinins in vitro. The difference may, however, partly depend on the experimental conditions and the detection limit of the tachykinin assay used. The protein extravasation response to capsaicin was absent after systemic capsaicin pretreatment, which causes a marked depletion of tachykinins in the ureter. In conclusion, capsaicin evokes release of several tachykinins from both central and peripheral endings of primary afferent neurons. The peptides released from sensory nerves in the periphery may induce effects such as protein extravasation and smooth muscle contraction.

Animals↗
PubMed1985

Reduced neurogenic inflammation in streptozotocin-diabetic rats due to microvascular changes but not to substance P depletion.

The effect of streptozotocin treatment (65 mg/kg i.v.) on plasma protein extravasation, nociception, and the content of substance P immunoreactivity (SP-IR) and somatostatin immunoreactivity (SOM-IR) was investigated in the rat. Twelve days after treatment, the neurogenic plasma extravasation induced by 5% mustard oil was reduced by 67% in the skin of the hind paw. Extravasation caused by SP, a putative mediator of neurogenic inflammation, was also reduced by 61% in the abdominal skin. While calcitonin gene-related peptide (CGRP) potentiated the SP-induced extravasation in control rats, no potentiation was observed in diabetic rats. Thermonociception or chemonociception was unchanged after streptozotocin treatment. The content of SP-IR and SOM-IR in sensory nerves or spinal ganglia was also not altered. These results indicate that the impairment of neurogenic inflammation in diabetic rats is not the result of depletion of neurogenic mediators like SP. Changes of the microvasculature at the leakage site appear to account for the effects observed.

Animals↗
PubMed1985

Potentiation of tachykinin-induced plasma protein extravasation by calcitonin gene-related peptide.

The effect of neuropeptides on plasma protein extravasation was investigated in the abdominal skin of rats. Substance P (SP), neurokinin A (NKA), and neurokinin B (NKB) induced extravasation with a threshold dose of about 1 pmol. Calcitonin gene-related peptide (CGRP) was ineffective up to 6 pmol. However, when CGRP was injected together with either of the tachykinins extravasation was potentiated. A dose of 6 pmol CGRP shifted the dose-response curve of SP to the left by a factor of about 100. The vasoconstrictor neuropeptide Y (NPY, 12 pmol) reduced the extravasation caused by SP or SP plus 6 pmol CGRP. These results indicate that all 3 tachykinins currently known to be present in sensory neurons induce plasma protein extravasation, i.e. mimic one sign of neurogenic inflammation. This activity is potentiated in the presence of CGRP which coexists with SP and NKA indicating that neurogenic inflammation may be augmented by these interactions.

Animals↗
PubMed1985

The spinal cord contains multiple factors causing plasma protein extravasation in the skin.

Nervous tissue was analyzed for possible mediators of neurogenic inflammation. Acid extracts of spinal cord or spinal roots contained activity causing plasma protein extravasation when injected into the rat abdominal skin. The activity was more than 1000-fold higher than could be attributed to the content of substance P (SP). It was not depleted from spinal cord after destruction of afferent C fibers by capsaicin and was resistant to proteolytic enzymes. The activity was clearly separated from SP or neurokinins by HPLC or gel filtration and was due to compounds of high polarity and low molecular weight. Further HPLC separated at least 6 peaks, two of which were found to contain adenosine and AMP, respectively, as active substances. The activity of these compounds and of the peaks was reduced by antihistaminics. A further compound identified was 5-HT. Thus, while several active non-peptidergic compounds were found, no clear evidence for a new mediator of neurogenic inflammation was obtained.

Adenosine↗
PubMed1985

Characterization of substance P-like immunoreactivity in submammalian species by high performance liquid chromatography.

Substance P-like immunoreactivity (SP-LI) as measured by RIA was found to be present in a variety of submammalian species and invertebrates. We analyzed this SP-LI in extracts from submammalian species by high performance liquid chromatography. The following species were investigated for the presence of SP-LI (RIA) which was further characterized by subsequent HPLC (investigated areas in parentheses): Hagfish (brain plus spinal cord), (brain, intestine, skin), frog (brain, intestine), turtle (brain, intestine), lizard (brain, intestine, skin) and mouse (spinal cord). RIA alone was performed in extracts from branchiostoma and cricket. The concentrations of SP-LI in brain, spinal cord and intestine of different submammalian species except branchiostoma brain and intestine and turtle brain, were in a similar range (2.1-5.3 fmol/mg in the brain, 0.2-2.0 fmol/mg in the spinal cord, 0.3-4.2 fmol/mg in the intestine). In the turtle brain, extremely high SP-LI concentrations (210 fmol/mg) were found, whereas brain and intestine of branchiostoma contained very little SP-LI (0.1 fmol/mg). In the skin of different species, SP-LI concentrations varied from 0.04 fmol/mg (trout) to 2.0 fmol/mg (lizard). In the cricket, high SP-LI concentrations were found in the cerebral ganglion (15 fmol/mg protein) and in the subesophageal ganglion (27 fmol/mg protein). HPLC analysis of extracts showed that all tissues investigated contained a substance which co-eluted with synthetic SP, and in most tissues a peak was present which co-eluted with SP sulfoxide. Only in mouse spinal cord, trout brain and hagfish brain were these the only peaks.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1984

[Physiology and physiopathology of substance P].

The neuropeptide substance P is considered a transmitter candidate of central and peripheral neurons, particularly of small diameter sensory afferents. Electrical stimulation of these fibers leads to release of substance P from the spinal cord. Since substance P injected intrathecally causes pain behaviour and since substance antagonists inhibit reactions to nociceptive stimuli, substance P is a likely transmitter of a population of nociceptive C-fibers. Release of substance P from the peripheral endings of these fibers leads to neurogenic inflammation, i.e. vasodilatation and protein extravasation. In the skin and eye substance P is involved in inflammatory reactions following thermal and chemical injuries. Similarly, stimulation of substance P fibers of the respiratory tract by various irritants causes mucosal edema and, at least in the guinea pig, also bronchoconstriction. Substance P antagonists inhibit neurogenic inflammation in animal experiments and may, applied topically, gain therapeutic value.

Eye↗
PubMed1983

Release of neurotensin from rat spinal cord in vitro.

The release of immunoreactive neurotensin (I-NT) from the dorsal half of the rat spinal cord was studied in vitro. A basal release in the order of 0.03-0.06% per min of tissue content was found. Depolarization with K+ caused a dose-dependent increase, with 60 mM K+ causing a 7.7-fold stimulation of release. This K+-evoked release was strictly calcium-dependent. Veratridine (50 microM) produced a 4.9-fold increase which was inhibited by 0.3 microM tetrodotoxin. Noradrenaline, 5-hydroxytryptamine, glutamate, kainic acid, N-methyl-D-aspartate, or quisqualate did not stimulate release of I-NT. The results support a role of NT as a neurotransmitter or modulator in the spinal cord.

Amino Acids↗
PubMed1982

Capsaicin applied to peripheral nerve inhibits axoplasmic transport of substance P and somatostatin.

Capsaicin was applied locally to the sciatic or saphenous nerve, and the effects on axoplasmic transport, neurogenic plasma extravasation, and thermal pain were studied. Capsaicin (10 mg/ml) led to a complete block of axoplasmic transport of immunoreactive substance P (I-SP) and somatostatin (I-SRIF) in rat sciatic nerve without affecting the transport of noradrenaline or acetylcholinesterase. Inhibition of I-SP transport was also found in sciatic nerves of guinea-pig, cat and rabbit. In contrast, one or two weeks after systemic capsaicin treatment (125 mg/kg s.c.), orthograde transport of I-SP was the same in control and capsaicin-treated rats. After local capsaicin application to the sciatic nerve, a decrease of I-SP was found not only in skin and sciatic nerve distal to the site of application, but also in dorsal root ganglia, dorsal roots and the dorsal half of the spinal cord segments L 4-5. This was accompanied by a loss of acid phosphatase activity in the substantia gelatinosa supplied by sciatic nerve afferents. Plasma extravasation by mustard oil was reduced in the skin of the hind paw with a time course identical to the I-SP depletion. The response to noxious heat (hot plate test) was, however, abolished earlier. These results indicate that capsaicin applied to a peripheral nerve inhibits axoplasmic transport in sensory but not in adrenergic or cholinergic neurons, which leads to long-term biochemical and functional changes of the entire sensory neuron. In addition, capsaicin appears to inhibit impulse propagation in certain populations of sensory neurons.

Acetylcholinesterase↗
PubMed1982

Capsaicin and nociception in the rat and mouse. Possible role of substance P.

Newborn or adult rats and mice were treated with capsaicin. The effect of systemic or intrathecal treatment on thermonociception, chemonociception, content and release of immunoreactive substance P (I-SP) was investigated. Treatment of two day old rats caused a small, but life-long elevation of the hot plate or tail withdrawal latency. Treatment of adult rats led to a large increase in the reaction time on the hot plate for 4--10 days but the tail withdrawal latency was only slightly elevated for not more than 1--2 days. Mice treated on the 2nd day of life had normal reaction times on the hot plate and a small and inconsistent prolongation of the tail withdrawal latency. In contrast, mice treated on day 7, 10 or as adults had greatly prolonged latencies in both tests for at least 3 months. The changes in latencies were not affected by naloxone or methysergide. Responses to noxious chemical stimuli were moderately inhibited in mice treated on the 2nd day of life, but almost abolished in mice treated on day 7, 10 or as adults. Neonatal capsaicin treatment of rats resulted in a depletion of I-SP in spinal cord and sciatic nerve for 20 months. Capsaicin-evoked release of I-SP from rat spinal cord was reduced by 93% after neonatal treatment, but only by 69% 2 weeks after adult treatment. Treatment of mice on day 2 caused a similar decrease of the I-SP content in spinal cord and of the capsaicin-evoked I-SP release (88%) as treatment on day 4 or 7 although behavioral changes were different. After treatment of adult mice release of I-SP was reduced by 93%. Capsaicin administered intrathecally to rats or mice depleted I-SP in the spinal cord but not in the sciatic nerve. The animals were almost insensitive to noxious heat (tail withdrawal test) and to local application of mustard oil or capsaicin to the hindpaw. Chemosensitivity of the eye, however, remained unchanged. The experiments indicate that systemic or intrathecal capsaicin treatment of rats or mice affects thermo- and chemonociception but species differences were found. It appears, furthermore, that changes in substance P alone cannot explain all the observed behavioral effects after capsaicin treatment.

Animals↗
PubMed1981

Substance P in the argentaffin carcinoid of the caecum: biochemical and biological characterization.

An argentaffin carcinoid tumour of the caecum which contained serotonin (167 micrograms/g) and consisted predominantly of EC1-cells, was analysed for the presence of peptides using immunohistochemical, biochemical and pharmacological methods. A very high content of 3.9 micrograms/g of immunoreactive substance P was found. The distribution of cells staining positively for substance P matched that of cells containing serotonin. While some immunoreactive somatostatin (3.2 ng/g) was present in the tumour, neurotensin, glucagon, gastrin, and motilin were not found. Part of the substance P immunoreactivity measured most likely represents authentic substance P: it behaved like substance P in two chromatographic systems and in two bioassays, and its activity on the guinea pig ileum was abolished by specific tachyphylaxis towards substance P.

Carcinoid Tumor↗
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↗