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Biomedical subjects

J Szolcsanyi

Publications and source records attributed to J Szolcsanyi.

14 recordsLinked to original sources
PubMed2005

Sumatriptan causes parallel decrease in plasma calcitonin gene-related peptide (CGRP) concentration and migraine headache during nitroglycerin induced migraine attack.

Sumatriptan-induced changes in plasma calcitonin gene-related peptide (CGRP) concentration and headache intensity were investigated in 19 female migraineurs during nitroglycerin-induced migraine attack. Sumatriptan nasal spray was administered 120 min after the onset of the attack. Blood samples were obtained immediately before and 60 min after sumatriptan administration. In those subjects whose migraine attack improved considerably 60 min after the treatment the plasma CGRP concentration decreased significantly (P<0.05). In contrast, plasma CGRP concentration failed to change in patients whose headache did not improve. In addition, plasma CGRP concentrations showed significant positive correlations with the headache scores both 60 and 120 min after sumatriptan administration (P<0.05). According to our results plasma CGRP concentration decreases parallel to headache intensity during sumatriptan treatment and this decrease in CGRP predicts effectiveness of antimigraine drug therapy. This supports that one of the main effects of triptans is to decrease CGRP release.

Biomarkers↗
PubMed2001

Functional and biochemical evidence for capsaicin-induced neural endothelin release in isolated working rat heart.

In isolated working rat heart, capsaicin elicited a concentration-dependent constriction of coronary arteries accompanied by decline of all cardiac parameters recorded (heart rate, coronary and aortic flow, left ventricular developed pressure, and first derivative of left ventricular developed pressure). The following evidence suggests that capsaicin-induced changes are mediated by endothelin of neural origin: (1) the capsaicin (10 nM)-evoked decrease in coronary flow resulting in deterioration of cardiac functions was mimicked by endothelin (0.1 nM); (2) the selective endothelin ET(A) receptor antagonist, cyclo (D-alpha-aspartyl-L-propyl-D-valyl-L-leucyl-D-tryptophyl) (1 microM), abolished the cardiac effects provoked by capsaicin (10 nM); (3) reduction of extracellular Ca2+ concentration from 2.4 to 1.2 or 0.6 mM inhibited the cardiac effects of capsaicin (10 nM) but not those induced by endothelin (0.1 nM); (4) perfusion of the heart with 0.1% (v/v) Triton X-100 damaged the endothelium and reversed the enhancement of coronary flow evoked by bethanechol (1 microM), decreased the basal flow, but was without effect on capsaicin-induced coronary constriction; (5) in response to capsaicin challenge (10-100 nM), the endothelin concentration measured in coronary effluent by means of radioimmunoassay increased up to sevenfold but remained unchanged in the presence of 0.6 mM Ca2+; (6) no reduction of coronary flow was induced by capsaicin (100 nM) applied to the heart of rats which were desensitised by capsaicin (150 mg/kg). It is concluded that, in the rat heart, capsaicin acting on VR1 capsaicin receptors elicits a release of endothelin from the sensory nerve terminals.

Analysis of Variance↗
PubMed1999

Decreased sensory neuropeptide release from trachea of rats with streptozotocin-induced diabetes.

We studied the release of somatostatin, calcitonin gene-related peptide (CGRP) and substance P in response to electrical field stimulation from isolated tracheas of rats following 4 weeks of streptozotocin (50 mg/kg i.v.)-induced diabetes. Field stimulation (40 V, 0.1 ms, 10 Hz for 120 s) increased the release of somatostatin, CGRP and substance P from the baseline 0.18+/-0.029, 0.17+/-0.027, and 1.77+/-0.086 to 0.51+/-0.022, 0.69+/-0.115, and 5.96+/-0.377 in control preparations and 0.31+/-0.081, 0.41+/-0.142, and 3.14+/-0.443 fmol/mg wet tissue weight in preparations from diabetic rats as measured by radioimmunoassay (control vs. diabetic P<0.01 for each). The results show a simultaneous decrease in release of the three sensory neuropeptides and an enhanced plasma somatostatin level in rats with streptozotocin-induced diabetes.

Animals↗
PubMed1999

Interaction between capsaicin and nitrate tolerance in isolated guinea-pig heart.

Capsaicin-induced increases in heart rate and coronary flow were blocked by N(G)-nitro-L-Arg-methyl ester (30 mM) in Langendorff-perfused guinea-pig hearts. Neither heart rate nor coronary flow changed by capsaicin in hearts from animals made tolerant to the hypotensive effect of 30 microg/kg nitroglycerin by the administration of 50 mg/kg nitroglycerin subcutaneously 4 times a day over 3 days. We conclude that the effector function of sensory nerves may deteriorate in nitrate tolerance.

Animals↗
PubMed1999

Interplay between nitric oxide and CGRP by capsaicin in isolated guinea-pig heart.

Capsaicin at a concentration of 10(-7)m induced a significant increase in heart rate and increased coronary flow in isolated Langendorff-perfused guinea-pig hearts. This effect was completely blocked by 30 microm of N(omega)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase. Additional incubation with 3 m m L-Arg antagonized the inhibitory effect of L-NAME. In the presence of 1 microm of a human calcitonin gene-related peptide fragment (hCGRP 8-37), a CGRP-receptor antagonist, L-Arg was without effect. We conclude that a capsaicin-induced increase in coronary flow and heart rate is dependent from an interplay between CGRP and NO in guinea-pig hearts. 1999 Academic Press.

Animals↗
PubMed1991

Inhibition of [3H]resiniferatoxin binding to rat dorsal root ganglion membranes as a novel approach in evaluating compounds with capsaicin-like activity.

We have recently reported the specific binding of [3H]resiniferatoxin to sensory ganglion membranes; this binding appears to represent the postulated vanilloid (capsaicin) receptor. In the present report, we compare the structure/activity relations for binding to rat dorsal root ganglion membranes and for biological responses in the rat, using a series of vanilloids of the capsaicin (homovanilloyl-decylamide, homovanilloyl-dodecylamide, homovanilloyl-cyclododecylamide, homovanilloyl-hexadecylamide, homovanilloyl-piperidine and nonenoyl-homoveratrylamide) and resiniferatoxin (tinyatoxin, 12-deoxyphorbol 13-phenylacetate 20-homovanillate) classes. We find that all the tested biologically active vanilloids, but not the inactive structure analogs, compete for the [3H]resiniferatoxin binding sites in rat dorsal root ganglion membranes, and we conclude that the [3H]resiniferatoxin binding assay may provide an efficient approach for evaluating such compounds. We also provide evidence that the [3H]resiniferatoxin receptor is likely to recognize vanilloids which are inserted into the membranes; and that the apparent activity of capsaicinoids may be significantly influenced by factors other than equilibrium binding affinities.

Animals↗
PubMed1990

Resiniferatoxin: an ultrapotent selective modulator of capsaicin-sensitive primary afferent neurons.

Resiniferatoxin (RTX) has been shown to function as an ultrapotent analog of capsaicin. It is reported here that RTX, like capsaicin, acts selectively on primary sensory neurons in rats to produce ultrastructural alterations and calcitonin gene-related peptide depletion. To evaluate RTX actions on capsaicin-sensitive nociceptors of vagal origin in the lung, the activation and desensitization of the pulmonary chemoreflex in both rats and cats were examined. In rats, RTX (2 ng-5 micrograms/kg i.v.) failed to elicit the full reflex triad (apnea, systemic hypotension and bradycardia); RTX did, however, desensitize the pulmonary chemosensitive receptors to capsaicin and phenyldiguanide. This effect is not achievable upon acute capsaicin treatment. RTX pretreatment (300 micrograms/kg s.c.) of rats also abolished the neurogenic edema formation, another response mediated via capsaicin-sensitive vagal fibers, in rat trachea to challenge either by capsaicin or ether. The effect of electrical stimulation of vagal nerve was not impaired after RTX injection, indicating that RTX desensitized only the capsaicin-sensitive pathway whereas the parasympathetic pathway remained unaltered. In cats, unlike in the rat, the full pulmonary chemoreflex occurred in response to 0.1 micrograms/kg RTX. It is concluded that RTX is a selective probe for capsaicin-sensitive neural pathways but the spectrum of action of the two compounds is not identical. The failure of RTX to provoke the pulmonary chemoreflex in the rat, which is the main limiting factor in the use of capsaicin, suggests a further advantage to the use of RTX for probing capsaicin-sensitive neural pathways.

Animals↗
PubMed1988

Selective excitation by capsaicin of mechano-heat sensitive nociceptors in rat skin.

The effect of close-by arterial injections of capsaicin on single afferent fibers of the saphenous nerve was studied on 82 units from control rats and on 44 units from rats pretreated with capsaicin (total dose 200 mg/kg applied subcutaneously under anesthesia 3 days before the experiment). In control rats low doses of capsaicin selectively excited mechano-heat sensitive cutaneous nociceptors (polymodal C fiber nociceptors and MH-A delta nociceptors). The median threshold dose for polymodal nociceptors was 0.1 micrograms. Repeated injections of capsaicin in near-threshold doses evoked reproducible effects without obvious signs of desensitization. In contrast A delta high-threshold mechanoreceptors, hair follicle receptors, cold receptors and C fiber mechanoreceptors were not excited by capsaicin even at doses of 5 micrograms. These high doses activated, however, some SA-II mechanoreceptors after a time lag, probably due to increased tissue turgor induced by plasma extravasation. Systemic capsaicin pretreatment of adult rats resulted in a selective decrease in the proportion of polymodal nociceptors among the afferent C-units, and an increment in the threshold dose of capsaicin of the responding polymodal nociceptors. It is concluded that in the adult rat capsaicin exerts a selective stimulatory and blocking effect on cutaneous mechano-heat sensitive nociceptors conducting both in the C fiber and A delta fiber range.

Animals↗
PubMed1987

Electrically evoked skin vasodilatation: a quantitative test of nociceptor function in man.

Direct stimulation of intact forearm skin affects adjacent microvascular blood flux. Pulses of current, known to activate C-fibres effectively, were applied over a period of 1-16 seconds at 2 Hz using transcutaneous stimulation. An increase of up to 50% was observed in skin microvascular blood flux. Increased blood flux correlated well with increasingly painful sensations. Some subjects responded to one or two pulses at 2 Hz, 0.5 ms in duration and 150 volts. A response onset latency of 4-15 s, lasting up to 5 minutes, was recorded. At higher frequencies (4-8 Hz) and more pulses (16-32) vasoconstriction was frequently observed before the usual flux increase. After administration of local anaesthesia (2% ligocaine) the resting skin blood flux increased, but electrical stimulation still produced vasodilatation. The local cutaneous flare response to electrical stimulation was abolished or greatly reduced by capsaicin pretreatment. Excitation of small intracutanous forearm nerve C-fibres produces increased microvascular blood flux which is dependent on local release of vasodilator substances. Thus the neurogenic flare (axon reflex) may have a physiological role in regulating skin blood flow, and nociceptor function may be measured by applying the aforementioned transcutaneous electrical stimulation.

Axons↗
PubMed1984

Action of intrathecal capsaicin and its structural analogues on the content and release of spinal substance P: selectivity of action and relationship to analgesia.

Intrathecal injections of capsaicin (CAP) and 4 other homovanillic acid (HMV) derivatives related to the structure of CAP were carried out. Capsaicin, 1-nonenoylvanillylamide (NVA), HMV-dodecylamide (DCA) (but not HMV-cyclohexylamide (CHA) or HMV-hexadecylamide (HDC] reduced the spinal content of substance P (SP), as measured by radioimmunoassay (RIA), and increased the tail-flick latency. Similar injection of kainic acid and piperine reduced levels of SP but failed to affect the tail-flick latency. None of the agents used affected spinal levels of cholecystokinin (CCK) or vasoactive intestinal peptide (VIP) as measured by RIA. In experiments using in vivo superfusion of the rat spinal cord, CAP, DCA and NVA were found to stimulate release of SP. Capsaicin had no effect on the levels of CCK or VIP immunoreactivity in the spinal superfusate. A tachyphylaxis to the effect of CAP and DCA on spinal SP release was demonstrated. Pretreatment with either agent blocked the releasing effect of the second. Pretreatment with an inactive analogue (HDC) had no effect on the subsequent activity of CAP. Kainic acid and piperine did not induce release of SP from the spinal cord. The relative selectivity of spinally administered capsaicinoids with regard to their effects on the content and release of peptides known to be contained in primary afferents and the presence of a similar structure-activity relationship for depletion and release of SP, desensitization and antinociception suggest the presence of a specific receptor site associated with a specific population of primary afferents through which pain information may pass. Whether SP is an 'afferent pain transmitter' is not clear, but at the least, it appears to serve as a marker for a population of afferents acted upon by spinally administered capsaicinoids.

Animals↗
PubMed1983

Effect of intrathecal capsaicin analogues on the immunofluorescence of peptides and serotonin in the dorsal horn in rats.

The intrathecal administration of capsaicin, a homovanillylamide derivative, has been demonstrated to cause analgesia in response to thermal stimuli. This analgesia has been correlated with a profound depletion of spinal substance P, a putative primary afferent transmitter. We studied the effects of capsaicin, a series of capsaicin analogues, piperine and kainic acid on the immunohistochemical staining of substance P, cholecystokinin, somatostatin, methionine-enkephalin and serotonin. Capsaicin and an analogue 1-nonenoyl-vanillylamide significantly elevated the tail flick latency and when the spinal cords of the rats were analyzed immunohistochemically, a profound depletion of substance P and cholecystokinin was observed. The spinal somatostatin-immunoreactivity of these rats was slightly reduced. Piperine also depleted substance P and reduced somatostatin staining but did not alter the staining intensity or density of cholecystokinin, methionine-enkephalin or serotonin. Kainate-depleted methionine-enkephalin but did not alter any other neuropeptides studied or serotonin. These results may indicate a link between capsaicin-induced analgesia and the concomitant depletion of cholecystokinin and substance P.

Alkaloids↗