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P Holzer

Publications and source records attributed to P Holzer.

At least 19 recordsLinked to original sources
PubMed1998

Mediation by 5_hydroxytryptamine of the femoral vasoconstriction induced by acid challenge of the rat gastric mucosa.

1. Gastric mucosal barrier disruption in the presence of luminal acid causes femoral vasoconstriction via a pathway that appears to be stimulated by messengers generated in the injured gastric mucosa. This study was undertaken to analyse the gastric factors that are responsible for the femoral vasoconstrictor response. 2. Gastric mucosal barrier disruption in the presence of luminal acid was induced by perfusing the stomach of urethane-anaesthetized rats with ethanol (15 %) in 0.01-0.15 M HCl. Blood flow in the left gastric and right femoral artery was estimated by the ultrasonic transit time shift technique. 3. Gastric perfusion of ethanol in HCl caused loss of H+ ions from the gastric lumen, decreased the HCO3- concentration in hepatic portal vein blood, induced macroscopic histological damage to the gastric mucosa, dilated the left gastric artery and constricted the femoral artery. These responses were related to the HCl concentration in the ethanol-containing perfusion medium. 4. The femoral vasoconstriction was also seen when, instead of ethanol, taurocholate (20 mM) was used to disrupt the gastric mucosal barrier in the presence of 0.15 M HCl. 5. The femoral vasoconstriction evoked by gastric perfusion of ethanol in HCl was left unaltered by pharmacological blockade of gastrin and histamine receptors. In contrast, the 5-hydroxytryptamine 5-HT1/2 receptor antagonist methiothepin, but not the 5-HT2A receptor antagonist ketanserin or the 5-HT3 receptor antagonist granisetron, inhibited the ability of both 5-hydroxytryptamine and gastric acid back-diffusion to constrict the femoral artery. 6. Gastric acid back-diffusion caused release of 5-hydroxytryptamine into the gastric lumen, which was related to the HCl concentration in the ethanol-containing perfusion medium. 7. These data show that femoral vasoconstriction evoked by gastric mucosal barrier disruption depends on back-diffusion of acid into the mucosa. The acid-induced damage results in release of 5-hydroxytryptamine from the gastric mucosa, and the pathway leading to constriction of the femoral artery involves 5-hydroxytryptamine acting via 5-HT1/2 receptors as a messenger molecule.

Animals↗
PubMed1998

Gastric acid-evoked c-fos messenger RNA expression in rat brainstem is signaled by capsaicin-resistant vagal afferents.

BACKGROUND & AIMS: Gastric acid is known to contribute to ulcer pain, but the mechanisms of gastric chemonociception are poorly understood. This study set out to investigate the pathways and mechanisms by which gastric acid challenge is signaled to the brain. METHODS: Neuronal excitation in the rat brainstem and spinal cord after intragastric administration of HCl (0.35-0.7 mol/L) was examined by in situ hybridization autoradiography for the immediate early gene c-fos. RESULTS: Gastric acid challenge did not induce c-fos transcription in the spinal cord but caused many neurons in the nucleus tractus solitarii and area postrema to express c-fos messenger RNA (mRNA). The HCl concentration-dependent excitation of medullary neurons was in part associated with behavioral manifestations of pain but not directly related to the acid-induced injury and contraction of the stomach. Subdiaphragmatic vagotomy suppressed the c-fos mRNA response to intragastric acid, and morphine inhibited it in a naloxone-reversible manner, whereas pretreatment of rats with capsaicin was without effect. CONCLUSIONS: Gastric acid challenge is signaled to the brainstem, but not the spinal cord, through vagal afferents that are sensitive to acid but resistant to capsaicin. It is hypothesized that the gastric acid-induced c-fos transcription in the brainstem is related to gastric chemonociception.

Afferent Pathways↗
PubMed1998

Neural emergency system in the stomach.

The maintenance of gastric mucosal integrity depends on the rapid alarm of protective mechanisms in the face of pending injury. Afferent neurons of extrinsic origin constitute an emergency system that is called into operation when the gastric mucosa is endangered by acid and other noxious chemicals. The function of these chemoceptive afferents can be manipulated selectively and explored with the excitotoxin capsaicin. Most of the homeostatic actions of capsaicin-sensitive afferents are brought about by peptides released from their peripheral endings in the gastric wall. When stimulated, chemoceptive afferents enhance gastric blood flow and activate hyperemia-dependent and hyperemia-independent mechanisms of protection and repair. In the rodent stomach, these local regulatory roles of sensory neurons are mediated by calcitonin gene-related peptide acting via calcitonin gene-related peptide 1 receptors and neurokinin A acting via neurokinin 2 receptors, with both peptides using nitric oxide as their common messenger. In addition, capsaicin-sensitive neurons form the afferent arc of autonomic reflexes that control secretory and motor functions of the stomach. The pathophysiological potential of the neural emergency system is best portrayed by the gastric hyperemic response to acid backdiffusion, which is signaled by afferent nerve fibers. This mechanism limits damage to the surface of the mucosa and creates favorable conditions for rapid restitution and healing of the wounded mucosa.

Animals↗
PubMed1998

Tachykinin NK1 and NK2 receptor-mediated control of peristaltic propulsion in the guinea-pig small intestine in vitro.

The tachykinins substance P and neurokinin A are excitatory cotransmitters of cholinergic enteric neurons, their actions being mediated by NK1, NK2 and NK3 receptors. This study examined which of these receptors are part of the neural circuitry of peristalsis. Peristaltic propulsion in luminally perfused segments of the guinea-pig isolated ileum was elicited by a rise of the intraluminal pressure. The pressure threshold at which peristaltic contractions were triggered was used to quantify drug effects on peristalsis, inhibition of peristalsis being reflected by an increase in the pressure threshold. The NK1, NK2 and NK3 receptor antagonists SR-140333, SR-48968 and SR-142 801 (each at 0.1 microM), respectively, had little effect on peristaltic activity as long as cholinergic transmission was left intact. However, both the NK1 and NK2 receptor antagonist (each at 0.1 microM) abolished peristalsis after cholinergic transmission via muscarinic receptors had been blocked by atropine (1 microM) and peristalsis rescued by naloxone (0.5 microM). When cholinergic transmission via nicotinic receptors was suppressed by hexamethonium (100 microM) and peristalsis restored by naloxone (0.5 microM), only the NK2 receptor antagonist (0.1 microM) was able to attenuate peristaltic performance as deduced from a rise of the peristaltic pressure threshold by 106%. The NK3 receptor antagonist (0.1 microM) lacked a major influence on peristalsis under any experimental condition. It is concluded that tachykinins acting via NK1 and NK2 receptors sustain intestinal peristalsis when cholinergic neuroneuronal and neuromuscular transmission via muscarinic receptors has been suppressed. NK2 receptors help maintaining peristalsis once cholinergic neuroneuronal transmission via nicotinic receptors has been blocked, whereas NK3 receptors play little role in the neural pathways of peristalsis.

Animals↗
PubMed1998

Neurogenic vasodilatation and plasma leakage in the skin.

1. Primary afferent nerve fibers control cutaneous blood flow and vascular permeability by releasing vasoactive peptides. These vascular reactions and the additional recruitment of leukocytes are commonly embodied in the term neurogenic inflammation. 2. Calcitonin gene-related peptide (CGRP) acting via CGRP1 receptors is the principal transmitter of neurogenic dilatation of arterioles whereas substance P (SP) and neurokinin A (NKA) acting via NK1 receptors mediate the increase in venular permeability. 3. Neurogenic vasodilatation and plasma protein leakage play a role in inflammation because many inflammatory and immune mediators including interleukin-1 beta, nitric oxide, prostanoids, protons, bradykinin, histamine, and 5-hydroxytryptamine can stimulate peptidergic afferent nerve fibers or enhance their excitability. 4. Neurogenic inflammatory reactions can be suppressed by alpha 2-adrenoceptor agonists, histamine acting via H1 receptors, 5-hydroxytryptamine acting via 5-HT1B receptors, opioid peptides, and somatostatin through prejunctional inhibition of peptide release from vasoactive afferent nerve fibers. CGRP, SP, and NKA receptor antagonists are powerful pharmacological tools to inhibit neurogenic inflammation at the postjunctional level. 5. Imbalance between the facilitatory and inhibitory influences on afferent nerve activity has a bearing on chronic inflammatory disease. Impaired nerve function represents a deficit in skin homeostasis while neuronal overactivity is a factor in allergic and hyperreactive disorders of the skin.

Animals↗
PubMed1998

Differential regulation of mesenteric and femoral blood flow in the rat as revealed by computerized data acquisition and evaluation.

1. A set-up for computerized acquisition and evaluation of haemodynamic data was constructed. Blood flow (BF) in the superior mesenteric and femoral artery of urethane-anaesthetized rats was measured with the ultrasonic transit time shift technique. The signals for arterial blood pressure and BF were fed into a personal computer via an analogue-digital converter. Mean arterial blood pressure, heart rate and vascular conductance (CV) were calculated on-line. For subsequent analysis of the data, algorithms were programmed to filter the data, and to determine average and peak values for each parameter. 2. Systemic hypertension induced by phenylephrine (3-300 nmol kg-1), angiotensin II (0.1-3.0 nmol kg-1) and arginine vasopressin (0.03-1.0 nmol kg-1) was accompanied by constriction of the mesenteric artery. In contrast, the femoral artery responded to phenylephrine with constriction, to angiotensin II with dilatation and to arginine vasopressin with dilation followed by constriction. The haemodynamic effects of endothelin-1 (0.03-3.0 nmol kg-1) were generally biphasic, the initial hypotension being associated with dilatation, and the delayed hypertension being accompanied by constriction of both the mesenteric and femoral arterial bed. 3. Terbutaline (3-1.0 nmol kg-1) and calcitonin gene-related peptide (0.03-1 nmol kg-1) caused systemic hypotension along with mesenteric and femoral vasodilatation. 4. Telmisartan (1 mg kg-1), an angiotensin AT1 receptor antagonist, dilated the mesenteric artery, but had no effect on femoral VC. In contrast, the alpha 1-adrenoceptor antagonist prazosin (0.1 mg kg-1), dilated the femoral artery without altering mesenteric VC. Similarly, the beta-adrenoceptor antagonist propranolol (1 mg kg-1) had no effect on mesenteric VC, but constricted the femoral arterial bed. 5. These data demonstrate that the haemodynamic effects of exogenously administered drugs can widely differ between the mesenteric and femoral arterial beds of urethane-anaesthetized rats. Furthermore, vascular tone of these two arterial beds in maintained by different vasoconstrictor systems. While the femoral artery is mainly under adrenergic control, the renin-angiotensin axis is predominant in the mesenteric arterial bed. In addition, this study also demonstrates that computerized analysis enables quick and accurate estimation of haemodynamic drug effects, and is superior to 'by hand' evaluation of peak changes in the functional diameter of the vascular bed under study.

Angiotensin II↗
PubMed1998

Neural injury, repair, and adaptation in the GI tract. II. The elusive action of capsaicin on the vagus nerve.

Capsaicin is an excitotoxin for primary afferent neurons, and perivagal administration of capsaicin is frequently used to ablate afferent fibers from the vagus nerve in an attempt to elucidate the role of afferent fibers in gastrointestinal (GI) regulation. However, this method has recently been called into question by research demonstrating that the molecular target of capsaicin on spinal and trigeminal afferents, vanilloid receptor subtype 1 (VR1), is absent from vagal afferents. Although some concerns about selectivity exist, the available information suggests that perineural capsaicin defunctionalizes afferent neurons of the vagus nerve by acting on a vanilloid receptor subtype that is structurally different from VR1.

Afferent Pathways↗
PubMed1997

Inhibition of acid-induced hyperaemia in the rat stomach by endogenous NK2 receptor ligands.

Since exogenously applied tachykinins (substance P and neurokinin A) prevent the neurogenic hyperaemia which is elicited by acid back-diffusion in the rat stomach, we investigated whether endogenous tachykinins would act in a similar manner. Acid back-diffusion, induced by perfusing the stomach with 15% ethanol in the presence of 0.05 M HCI, increased gastric mucosal blood flow (GMBF) by 60-100% as determined by hydrogen clearance in urethane-anaesthetized rats. This response remained unchanged after pretreatment with the tachykinin NK1 receptor antagonist SR 140,333 (300 nmol/kg) but tended to be enhanced by the NK2 receptor antagonist MEN 10,627 (200 nmol/kg). When given during ongoing acid back-diffusion, MEN 10,627 significantly enhanced the acid-evoked vasodilatation as compared with vehicle or SR 140,333. We conclude that endogenously released tachykinins, acting via NK2 receptors, limit the gastric hyperaemic response to acid.

Animals↗
PubMed1997

Involvement of nitric oxide in the substance P-induced inhibition of intestinal peristalsis.

Although considered as an intestinal motor stimulant, substance P can inhibit intestinal peristalsis via stimulation of tachykinin NK1 receptors. Since NK1 receptors are present on enteric nitrergic neurones, the contribution of nitric oxide (NO) to the peristaltic motor inhibition caused by tachykinins was examined in luminally perfused segments of isolated guinea-pig ileum. Substance P (100 nM) and the NK1 receptor agonist substance P methyl ester (100 nM) increased the intraluminal pressure threshold at which peristaltic contractions were elicited. This inhibitory influence on peristalsis was prevented by the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (300 microM) in an enantiomer-selective manner. It is concluded that the substance P/NK1 receptor-mediated depression of intestinal peristalsis involves inhibitory motor pathways utilizing NO as a transmitter.

Animals↗
PubMed1997

Tachykinins in the gut. Part I. Expression, release and motor function.

The preprotachykinin-A gene-derived peptides substance P and neurokinin (NK) A are expressed in distinct neural pathways of the mammalian gut. When released from intrinsic enteric or extrinsic primary afferent neurons, tachykinins have the potential to influence both nerve and muscle by way of interaction with three different types of tachykinin receptor, termed NK1, NK2 and NK3 receptors. Most prominent among the effects of tachykinins is their excitatory action on gastrointestinal motor activity, which is seen in virtually all regions and layers of the mammalian gut. This action depends not only on a direct activation of the muscle through NK1 and/or NK2 receptors, but also on stimulation of excitatory enteric motor pathways through NK3 and/or NK1 receptors. In addition, tachykinins can inhibit motor activity by stimulating either inhibitory neuronal pathways or interrupting excitatory relays. A synopsis of the available data indicates that endogenous substance P and NKA interact with other enteric transmitters in the physiological control of gastrointestinal motor activity. Derangement of the regulatory roles of tachykinins may be a factor in the gastrointestinal dysmotility associated with infection, inflammation, stress and pain. In a therapeutic perspective, it would seem conceivable, therefore, that tachykinin agonists and antagonists are adjuncts to the treatment of motor disorders that involve pathological disturbances of the gastrointestinal tachykinin system.

Animals↗
PubMed1997

Tachykinins in the gut. Part II. Roles in neural excitation, secretion and inflammation.

The preprotachykinin-A gene-derived peptides substance (substance P; SP) and neurokinin (NK) A are expressed in intrinsic enteric neurons, which supply all layers of the gut, and extrinsic primary afferent nerve fibers, which innervate primarily the arterial vascular system. The actions of tachykinins on the digestive effector systems are mediated by three different types of tachykinin receptor, termed NK1, NK2 and NK3 receptors. Within the enteric nervous system, SP and NKA are likely to mediate, or comediate, slow synaptic transmission and to modulate neuronal excitability via stimulation of NK3 and NK1 receptors. In the intestinal mucosa, tachykinins cause net secretion of fluid and electrolytes, and it appears as if SP and NKA play a messenger role in intramural secretory reflex pathways. Secretory processes in the salivary glands and pancreas are likewise influenced by tachykinins. The gastrointestinal arterial system may be dilated or constricted by tachykinins, whereas constriction and an increase in the vascular permeability are the only effects seen in the venous system. Various gastrointestinal disorders are associated with distinct changes in the tachykinin system, and there is increasing evidence that tachykinins participate in the hypersecretory, vascular and immunological disturbances associated with infection and inflammatory bowel disease. In a therapeutic perspective, it would seem conceivable that tachykinin antagonists could be exploited as antidiarrheal, antiinflammatory and antinociceptive drugs.

Animals↗
PubMed1997

Gastric mucosal blood flow regulation in response to different stimuli.

We compared changes in gastric mucosal blood flow (GMBF) and left gastric artery blood flow (LGABF) in response to pharmacological, physiological, and pathological stimuli. GMBF and LGABF were measured by the hydrogen gas clearance and perivascular ultrasonic transit time techniques, respectively, under baseline conditions and following intravenous infusion of vasopressin or pentagastrin, isovolemic hemodilution, or gastric perfusion with HCl-taurocholate. Blood flow changes following vasopressin or hemodilution were significantly larger in the left gastric artery than in the gastric mucosa. In contrast, the increment in blood flow associated with pentagastrin-stimulated acid secretion was significantly greater in the gastric mucosa than in the extramural artery. Barrier disruption with acid-taurocholate induced similar changes in both measurement sites. The gastric hyperemia induced by either mechanism was significantly attenuated by blockade of NO synthesis. These data demonstrate that although functional changes in GMBF are primarily supported by changes in blood flow at the extramural gastric arteries, the gastric mucosal microvasculature is also under the influence of independent local control mechanisms.

Anemia↗
PubMed1997

Nitric oxide-dependent and -independent vascular hyporeactivity in mesenteric arteries of portal hypertensive rats.

1. Increased production of nitric oxide (NO) has been suggested to underlie both the vascular hyporeactivity to vasoconstrictors and the splanchnic vasodilatation seen in portal hypertension. This study assessed the role of NO in the vasoconstrictor hyporeactivity of portal vein-ligated (PVL) rats in isolated and in situ perfused mesenteric arterial beds. 2. Isolated perfused mesenteric arteries of PVL rats were significantly less reactive to noradrenaline (NA), methoxamine (METH), arginine vasopressin (AVP) and endothelin-1 (ET-1) than those from sham-operated (Sham) rats. 3. Blockade of NO synthesis with NG-nitro-L-arginine methyl ester (L-NAME, 100 microM) in isolated perfused mesenteric arteries from PVL rats restored the reactivity to bolus injections of AVP and ET-1, but had little effect on the hyporeactivity to NA or METH. Cyclo-oxygenase inhibition with indomethacin (5 microM) likewise did not restore reactivity to METH of isolated perfused mesenteric arteries of PVL rats. 4. The hyporeactivity to METH seen in isolated perfused mesenteric arteries from PVL rats was reduced by low concentrations of AVP (20 nM) or ET-1 (1 nM) which per se caused only a slight increase in perfusion pressure. When L-NAME (100 microM) was combined with AVP (20 nM) or ET-1 (1 nM), respectively, reactivity to METH of isolated perfused mesenteric arteries of PVL rats was restored to the level seen in Sham rats. These effects of AVP and ET-1 were not mimicked by precontracting the vessels with 5-hydroxytryptamine (5 microM). 5. The differential effects of L-NAME and AVP on the hyporesponsiveness to methoxamine and AVP were corroborated by experiments performed with the in situ perfused mesenteric vascular bed preparation. 6. These data indicate that both NO-dependent and NO-dependent mechanisms are involved in the vasoconstrictor hyporesponsiveness of mesenteric arteries from portal hypertensive rats. The hyporeactivity to AVP and ET-1 is mediated by NO whereas the reduced responsiveness to adrenoceptor agonists appears to be predominantly NO-independent AVP and ET-1, in addition, seem to inhibit the NO-independent mechanism of vascular hyporeactivity, since the hyporesponsiveness to METH was reduced in the presence of AVP or ET-1 and abolished by the combination of these peptides with L-NAME.

Animals↗
PubMed1997

Dilatation by angiotensin II of the rat femoral arterial bed in vivo via pressure/flow-induced release of nitric oxide and prostaglandins.

1. The haemodynamic effects of angiotensin II (AII) and, for comparison, arginine vasopressin (AVP) in the femoral and superior mesenteric artery of urethane-anaesthetized rats were analysed with the ultrasonic transit time shift technique. 2. I.v. bolus injection of AII (0.1-3 nmol kg-1) and AVP (0.03-1 nmol kg-1) increased blood pressure which was accompanied by a decrease in blood flow through the superior mesenteric artery and an increase in femoral blood flow. The femoral hyperaemia was in part due to vasodilatation as indicated by a rise of femoral vascular conductance up to 200% relative to baseline. The femoral vasodilatation caused by AVP, but not AII, was followed by vasoconstriction. 3. Blockade of angiotensin AT1 receptors by telmisartan (0.2-20 mumol kg-1) prevented all haemodynamic responses to AII. 4. The femoral dilator responses to AII and AVP depended on the increase in vascular perfusion pressure since vasodilatation was reversed to vasoconstriction when blood pressure was maintained constant by means of a gravity reservoir. However, the AII-evoked femoral vasodilatation was not due to an autonomic or neuroendocrine reflex because it was not depressed by hexamethonium (75 mumol kg-1), prazosin (0.25 mumol kg-1) or propranolol (3 mumol kg-1). 5. The AII-induced femoral vasodilatation was suppressed by blockade of nitric oxide (NO) synthesis with NG-nitro-L-arginine methyl ester (L-NAME, 40 mumol kg-1) and reversed to vasoconstriction when L-NAME was combined with indomethacin (30 mumol kg-1), but was left unaltered by antagonism of endothelin ETA/B receptors with bosentan (37 mumol kg-1). 6. These results demonstrate that the effect of AII to increase systemic blood pressure and the resulting rise of perfusion pressure in the femoral artery stimulates the formation of NO and prostaglandins and thereby dilates the femoral arterial bed. This local vasodilator mechanism is sufficient to mask the direct vasoconstrictor response to AII.

Angiotensin II↗
PubMed1997

Dual excitatory and inhibitory effect of nitric oxide on peristalsis in the guinea pig intestine.

The implications of the enteric neurotransmitter nitric oxide (NO) in intestinal peristalsis were investigated. Propulsive motility in isolated segments of the guinea pig ileum was triggered by intraluminal fluid infusion to distend the intestinal wall, and the pressure threshold for eliciting peristaltic waves was used to quantify facilitation (decrease in threshold) or inhibition (increase in threshold) of peristalsis. The NO donor sodium nitroprusside (0.1-100 microM serosally) caused a prompt facilitation of peristalsis, which in the presence of a threshold concentration of atropine (10 nM) was followed by a concentration-related blockade of peristalsis. Further analysis showed that sodium nitroprusside (10 and 100 microM) first relaxed, then contracted, and finally relaxed the longitudinal muscle of the guinea pig isolated ileum, the contraction being blocked by atropine (1 microM). Inhibition of NO synthase by NG-nitro-L-arginine methylester (100-300 microM) facilitated peristalsis, an effect that was reduced by L-arginine (1 mM) but left unaltered by atropine (10 nM). Blockade of inhibitory neuromuscular transmission by successive exposure of the ileum to apemin (0.5 microM) and NG-nitro-L-arginine methylester (300 microM), in this or reverse order, disrupted the coordinated pattern of peristalsis and caused irregular nonpropulsive contractions of the circular muscle. It is concluded that NO has a dual excitatory and inhibitory effect on intestinal motility. The excitatory effect involves cholinergic motor neurons, whereas the inhibitory effect reflects relaxation of intestinal muscle. Abolition of peristalsis by combined exposure to NG-nitro-L-arginine methylester and apamin attests to an essential role of enteric inhibitory motor neurons in the coordination of propulsive motility in the intestine.

Animals↗
PubMed1997

Neurokinin A-induced vasoconstriction and muscular contraction in the rat isolated stomach: mediation by distinct and unusual neurokinin2 receptors.

This study examined the pharmacological identity of the tachykinin receptors which in the rat stomach mediate vasoconstriction and muscular contraction. The vasculature of the rat isolated stomach was perfused with oxygenated Krebs buffer containing 3% dextran. Vasoconstrictor responses were recorded as increases in the vascular perfusion pressure and gastric contractions were measured as increases in the intraluminal pressure. By examining the effects of selective agonists and antagonists for tachykinin neurokinin (NK)1, NK2 and NK3 receptors it was found that the vasculature contained only NK2 receptors that were activated by the NK2 receptor agonist [betaAla8]-NKA-(4-10) and inhibited by the NK2 receptor antagonists MEN-10,627 and GR-94,800. However, the vasoconstrictor action of NKA was blocked only when the preparations were exposed to a combination of NK1, NK2 and NK3 receptor antagonists (SR-140,333, MEN-10,627, PD-161,182). In contrast, the NKA-evoked contraction of the gastric musculature was suppressed by NK2 receptor antagonists but little affected by NK1 or NK3 receptor antagonists. This observation was consistent with the predominance of NK2 receptors on the muscle as revealed by the effects of receptor-selective NK1, NK2 and NK3 agonists and antagonists. These results demonstrate that the major tachykinin receptor type present on the gastric vasculature and musculature is a NK2 receptor that is sensitive to receptor-selective agonists and antagonists. The NKA-evoked gastric contraction is also primarily due to NK2 receptor activation, whereas the NKA-induced vasoconstriction is mediated by a distinct and unusual type of NK2-like receptor that is blocked by a combination of NK1, NK2 and NK3 receptor antagonists only.

Animals↗
PubMed1996

Differential expression of c-fos messenger RNA in the rat spinal cord after mucosal and serosal irritation of the stomach.

Expression of the immediate early gene c-fos is considered to be a marker for neuronal activation in the spinal cord in response to afferent input. Since the stomach is continually exposed to injurious chemicals, the present study examined whether application of acid (0.15 M HCl) and formalin (5%) to the gastric mucosa or serosal surface of the stomach stimulates c-fos transcription in the caudal thoracic spinal cord of anaesthetized rats. The spinal cord was removed 15, 45 or 120 min after exposure of the stomach to the noxious chemicals and processed for quantitative in situ hybridization autoradiography of c-fos messenger RNA. Exposure of the gastric mucosa to acid or formalin failed to increase the expression of c-fos messenger RNA in the thoracic spinal cord. Application of acid to the serosal surface of the stomach was also unable to stimulate c-fos transcription, whereas serosal application of formalin led to substantial expression of c-fos messenger RNA in the superficial but also deeper laminae of the spinal dorsal horn when examined 45 min, but not 15 or 120 min, post-stimulation. The highest expression of c-fos messenger RNA was seen when formalin was injected subcutaneously into one hindpaw and c-fos transcription was examined in the lumbar spinal cord. These data indicate that acute exposure of the gastric mucosa to chemical injury does not provide the afferent input which is necessary to cause appreciable c-fos transcription in second order neurons within the spinal cord. Stimulation of the gastric mucosa by acid and formalin was followed, however, by gastric hyperaemia in which spinal afferents releasing vasodilator peptides have been implicated. It is concluded, therefore, that acute stimulation of nociceptive afferents in the stomach causes local homoeostatic reactions but does not necessarily provide afferent input sufficient to recruit spinal nociceptive circuits.

Animals↗