Biomedical subjects

A Saria

Publications and source records attributed to A Saria.

At least 145 records · Page 8Linked to original sources

PubMed1987

Coexisting peptides in capsaicin-sensitive sensory neurons: release and actions in the respiratory tract of the guinea-pig.

Release of substance P (SP) and neurokinin A (NKA), was demonstrated in the isolated perfused guinea-pig lung. Significant release was obtained by perfusion with capsaicin, high potassium, histamine, bradykinin dimethylphenylpiperazinium, and by electrical vagal nerve stimulation. Capsaicin-induced peptide release was not blocked by 1 microM clonidine. SP and NKA contracted respiratory smooth muscle, NKA being 42 times more potent. Both tachykinins were equipotent in relaxing pulmonary artery. It is concluded that multiple tachykinin can be released from capsaicin-sensitive sensory nerves in the respiratory tract, exerting multiple effects on the target tissues.

Animals↗

PubMed1987

[Changes in nasal volume flow following local administration of neuropeptide substance P and capsaicin].

In a recently published paper, the author discovered the neuropeptide Substance-P (SP) in human nasal mucosa. SP is the transmitter substance of sensory neurons in the central and peripheral nervous system. The influence of SP and CAPSAICIN on the vascular system of human nasal mucosa is investigated. The application of these substances on the nasal mucosa of volunteers leads to a significant decrease of nasal air flow which can be registered by anterior rhinomanometry. The pathogenetic importance of vascular protein leakage and vasodilatation caused by the neuropeptide SP is discussed.

Capsaicin↗

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

Distribution and origin of substance P- and neuropeptide Y-immunoreactive nerves in the guinea-pig heart.

The localization and origin of substance P (SP)-, neuropeptide Y (NPY)-, and noradrenaline/tyrosine hydroxylase (NA/TH)- immunoreactive (IR) nerves in the guinea-pig heart were investigated by means of immunohistochemistry; quantitative analysis was performed by radio-immunoassay (NPY) and high performance liquid chromatography (NA). Both untreated animals and animals subjected to stellatectomy, combined stellatectomy and local capsaicin pretreatment of the vagal nerves or systemic application of capsaicin were studied. A dense network of SP-IR nerves was observed in the right atrium in different locations: (1) around local cardiac ganglion cells, (2) close to blood vessels, (3) within the myocardium, and (4) close to and within peri- and endocardium. A moderately dense SP-innervation, mainly related to blood vessels, was found in the ventricles. Very dense networks of NPY- and TH-IR nerve fibers with an overlapping distributional pattern around blood vessels and in the myocardium were seen in both the atria and the ventricles. In addition, some cell bodies in local cardiac ganglia were NPY-IR. Bilateral stellatectomy resulted in a reduction of SP-IR in the right atrium (55% of control), which was more pronounced after additional capsaicin pretreatment of the vagal nerves (44% of control). In the left ventricle no significant depletion of SP-IR was seen by either stellatectomy or combined stellatectomy and capsaicin treatment of the vagal nerves. It was not possible to establish any defined target areas within the heart for vagal or spinal SP-IR afferents by use of immunohistochemical methods. Systemic capsaicin treatment caused a total loss of SP-IR nerves in the heart.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1986

Reserpine-induced depletion of neuropeptide Y from cardiovascular nerves and adrenal gland due to enhanced release.

The mechanisms underlying reserpine-induced depletion of neuropeptide Y-like immunoreactivity (NPY-LI) in relation to tissue content of noradrenaline (NA) and cardiovascular impairment were studied in guinea-pigs. Reserpine pretreatment (5 mg/kg SC) caused a 5-fold increase in plasma levels of NPY-LI with a maximum after 4 h. This was associated with a progressive fall in systemic arterial blood pressure and heart rate (to about 50% of basal values). The contents of NPY-LI and NA in nerves of the heart and quadriceps muscle were then reduced by about 75% and 85%, respectively. The adrenal content of NPY-LI was reduced by 40% 8 h after reserpine, while the adrenaline content was uninfluenced. Pretreatment with guanethidine depleted NA in the heart but did not influence plasma levels or tissue content of NPY-LI per se. The reserpine-induced increase in plasma NPY-LI and the depletion of NPY-LI in the heart and skeletal muscle was to a large extent prevented by guanethidine. The reserpine-induced bradycardia and hypotension were reduced after guanethidine pretreatment. Chlorisondamine pretreatment depressed heart rate, blood pressure and plasma levels of NPY-LI. Furthermore, chlorisondamine inhibited the reserpine-induced increase in plasma NPY-LI and prevented the reduction in tissue content of NPY-LI in the heart, skeletal muscle and adrenal.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗

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↗

PubMed1986

Mechanisms underlying pre- and postjunctional effects of neuropeptide Y in sympathetic vascular control.

The effects of porcine neuropeptide Y (NPY) regarding sympathetic vascular control were studied in vitro on isolated rat blood vessels. The 10(-9)M NPY enhanced (about two-fold) the contractile responses to transmural nerve stimulation (TNS), noradrenaline (NA) and adrenaline (about two-fold) in the femoral artery. Higher concentrations of NPY (greater than 10(-8)M) caused an adrenoceptor-resistant contraction per se. The TNS-evoked [3H]NA efflux was significantly reduced by NPY in a concentration-dependent manner (threshold 10(-9)M). The calcium antagonist, nifedipine, abolished the contractile effects of NPY and the NPY-induced enhancement of NA contractions but did not influence the prejunctional inhibition of [3H]NA release. Receptor-binding studies showed that the ratio of alpha 1-to alpha 2-adrenoceptors in the femoral artery was 30:1. The NPY did not cause any detectable change in the number of alpha 1-or alpha 2-adrenoceptor binding sites or in the affinity of alpha 2-binding sites, as revealed by prazosin- and clonidine-binding, respectively. The NPY also inhibited the TNS-evoked [3H]NA release (by 42-86%) in the superior mesenteric and basilar arteries and in femoral and portal veins. The NPY still depressed TNS-evoked [3H]NA secretion from the portal vein in the presence of phentolamine. The NPY caused a clear-cut contraction in the basilar artery, increased the contractile force of spontaneous contractions in the portal vein, while only weak responses were observed in the superior mesenteric artery and femoral vein. The NA-induced contraction was markedly enhanced by NPY in the superior mesenteric artery, only slightly enhanced in the portal vein and uninfluenced in the femoral vein. In conclusion, in all blood vessels tested, NPY depresses the TNS-evoked [3H]NA secretion via a nifedipine-resistant action. Furthermore, NPY exerts a variable, Ca2+-dependent vasoconstrictor effect and enhancement of NA and TNS contractions.

Animals↗

PubMed1986

Autonomic mechanisms underlying capsaicin induced oral sensations and salivation in man.

The effects of capsaicin, citric acid and nicotine applied to the apex or radix of the tongue on taste sensations and salivation were studied in relation to the presence of substance P immunoreactive neurones in man. Application of capsaicin (30 micron) to the apex of the tongue or to the palatinal mucosa, but not to the radix of the tongue, caused a reproducible burning sensation and salivation from the submandibular-sublingual and parotid glands. The salivation response to capsaicin was reduced by methylscopolamine pretreatment. Similar levels of substance P immunoreactivity were present in the lingual apex and radix area (including vallate papillae) of man, while in the cat about 4 times higher levels of substance P immunoreactivity were present in the vallate papillae than in the lingual apex. Immunohistochemistry showed that in the cat many substance P immunoreactive nerves were associated with the taste buds of the vallate papillae, while in man substance P immunoreactive fibres were only seen penetrating into the epithelium of the lingual apex. In addition some subepithelial blood vessels in all regions were surrounded by substance P immunoreactive nerves in both cat and man. Citric acid application to the tongue apex caused both submandibular-sublingual and parotid salivary secretion concomitant with a burning sensation. Salivary secretion was also seen after citric acid application to the radix of the tongue. This response was associated with a sour taste. The salivation response to citric acid was not significantly reduced by methylscopolamine pretreatment. Lingual apex application of nicotine was associated with a sweet taste and a small rise in salivary secretion rate. This response was not significantly reduced by methylscopolamine. In conclusion, the sensitivity to capsaicin of the human tongue is restricted to the apex portion. This is in parallel with the occurrence of intraepithelial substance P immunoreactive nerve fibres. Capsaicin induced salivary secretion seems mainly to be mediated via parasympathetic, cholinergic reflex mechanisms. Citric acid and nicotine induced salivation responses are comparatively more resistant to methylscopolamine pretreatment.

Adolescent↗

PubMed1985

Neuropeptide Y (NPY) and peptide YY (PYY) inhibit prostaglandin E2-induced intestinal fluid and electrolyte secretion in the rat jejunum in vivo.

NPY, a recently discovered peptide consisting of 36 amino acids, is present in intrinsic intestinal nerves and in extrinsic noradrenergic nerves innervating intestinal blood vessels. We have investigated the influence of NPY and of the structurally related peptide YY (PYY) on the effect of PGE2-induced fluid and electrolyte secretion in the tied-off rat jejunum in vivo. Close intraarterial infusion of PGE2 (4.5-450 pmol X min-1) dose dependently reversed the net absorption of fluid, sodium and chloride into net secretion (P less than 0.01 for all three parameters). Additional i.a. infusion of NPY significantly inhibited the effect of PGE2 (45 pmol X min-1) on fluid transport at infusion rates of 0.4 and 4.0 pmol X min-1 (P less than 0.01). Infusion of 0.04 pmol X min-1 NPY was without effect. PGE2-induced sodium and chloride secretion were also significantly reduced by NPY at an infusion rate of 0.4 but not of 0.04 pmol X min-1. NPY alone was without any effect on fluid or electrolyte absorption in the controls. PYY, which is present in endocrine cells but not in nerves in the gut, was without effect at 0.4 pmol X min-1 and slightly but significantly reduced PGE2-induced fluid secretion at 4.0 pmol X min-1. It is concluded that NPY is a potent inhibitory factor in the neuronal control of intestinal fluid and electrolyte transport.

Animals↗

PubMed1985

Neurokinin A depolarizes neurons of the guinea pig inferior mesenteric ganglia.

Neurokinin A (NKA) applied either by superfusion (0.1-10 microM) or by pressure ejection evoked a slow membrane depolarization in neurons of the inferior mesenteric ganglia in vitro. The NKA-induced depolarization which was not significantly affected by reducing the Ca concentration or by tetrodotoxin was associated in most cases by a small-to-moderate increase in membrane resistance; however, conditioning hyperpolarization increased rather than decreased the response. The depolarization elicited by NKA was eliminated in the presence of substance P (SP) and the depolarization by SP in the presence of NKA. The results suggest that the actions of NKA on prevertebral neurons are similar to that of SP and that these two peptides may act on the same receptors or share similar ionic channels.

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

Differential effects of reserpine and 6-hydroxydopamine on neuropeptide Y (NPY) and noradrenaline in peripheral neurons.

The effects of 6-hydroxydopamine (6-OHDA) and reserpine pretreatment on peripheral neuropeptide Y (NPY)- and noradrenaline (NA)-containing neurons were studied in guinea-pigs. Ten days after 6-OHDA pretreatment, a 60-80% reduction of the NA content was observed in the right atrium of the heart, stellate ganglion and spleen. The content of NPY-like immunoreactivity (LI) was reduced by about 50% in the heart, not changed in the spleen while it increased to 200% of control in the stellate ganglion. Immunohistochemistry showed a pronounced loss of NPY- and tyrosinehydroxylase (TH)-immunoreactive (IR) nerves in the heart but not in the spleen. Increased NPY-IR was seen in axons and cell bodies of the stellate ganglion. Reserpine pretreatment (thereshold dose 0.5 mg X kg-1) caused a dose- and time-dependent reduction of the content of NPY-LI in the heart. A maximal depletion of NPY-LI (about 80%) was observed 5 days after reserpine. Reserpine pretreatment also reduced the content of NPY-LI in the spleen, while no significant change was observed in the adrenal gland or vas deferens. The levels of NPY-LI increased in the stellate ganglion to about 180% of control 5 days after reserpine. Immunohistochemical analysis revealed an almost total loss of NPY-IR nerve fibres in the heart as well as around blood vessels in the lung and skeletal muscle. No detectable changes were observed in perivascular NPY-IR nerves in the spleen, vas deferens or kidney. TH-IR nerves remained unchanged after reserpine, thus indicating that the observed loss of NPY-IR nerves was due to a depletion of NPY and not a degeneration. No change in the levels of substance P-LI was observed in the right atrium 5 days after reserpine. NA was, in contrast to NPY, markedly depleted in all tissues investigated after reserpine treatment. The depletion of NA was more extensive, and occurred more rapidly and at much lower doses as compared to the effects on NPY-LI. Ligations of the sciatic nerve revealed that NPY-LI was transported axonally with a rapid rate (3 mm/h). Reserpine pretreatment significantly increased the amount of accumulated NPY-IR above the ligation, suggesting an increase in axonal transport. High performance liquid chromatography revealed that the NPY-LI consisted of two major peaks in the stellate ganglia, while only one peak closely corresponding to porcine NPY was seen in the right atrium. In conclusion, 6-OHDA pretreatment depletes NPY-LI in certain terminal regions and increases NPY-LI in ganglia.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

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↗

PubMed1985

Mechanisms underlying changes in the contents of neuropeptide Y in cardiovascular nerves and adrenal gland induced by sympatholytic drugs.

Neuropeptide Y (NPY) is a recently isolated vasoactive peptide, which is present, together with catecholamines, in sympathetic nerves and in the adrenal medulla. In the present study, we report that pretreatment with sympatholytic agents influences the tissue levels of NPY-like immunoreactivity (NPY-LI) in the guinea-pig. Thus, 24 h after reserpine not only noradrenaline (NA), but also NPY-LI, was depleted in the heart, spleen and the adrenal gland. The levels of NPY-LI in the vas deferens and stellate ganglia, however, were unaffected by reserpine in spite of marked depletions of NA. The reserpine-induced depletion of NPY-LI was probably caused by enhanced nerve-impulse flow and subsequent release from cardiovascular nerves in excess of resupply, since it could be prevented by the ganglionic-blocking agent chlorisondamine. Long-term (6 days) treatment with chlorisondamine reduced the levels of NPY-LI in the stellate ganglion. Short-term treatment (48 h) with guanethidine partially prevented the reserpine-induced depletion of NPY-LI, probably due to inhibition of NPY release. Long-term guanethidine treatment depleted not only NA, but also NPY-LI from the spleen. Pretreatment with the alpha-receptor antagonist phenoxybenzamine did not influence the NA levels but reduced the content of NPY-LI in the spleen via a mechanism that was dependent on intact ganglionic transmission. Since NPY has several cardiovascular actions, changes in NPY mechanisms may contribute to the pharmacological and therapeutical effects of sympatholytic agents.

Adrenal Glands↗