Long-Term Blood Pressure Control Effect of Celiac Plexus Block with Botulinum Toxin.

Celiac plexus block (CPB) is one of the main treatment options for patients resistant to conventional antihypertensive drugs. We present a case of resistant hypertension (RHTN) that was treated with CPB using botulinum toxin. An 18-year-old male patient with RHTN, who suffered from persistent hypertension even after combination therapy and a renal denervation procedure, was referred to our pain center for CPB. CPB using botulinum toxin following the use of only local anesthetics resulted in control of systolic blood pressure (BP) at ~150 mmHg for at least three months.

Identifying the Source of a Humoral Factor of Remote (Pre)Conditioning Cardioprotection.

Signalling pathways underlying the phenomenon of remote ischaemic preconditioning (RPc) cardioprotection are not completely understood. The existing evidence agrees that intact sensory innervation of the remote tissue/organ is required for the release into the systemic circulation of preconditioning factor(s) capable of protecting a transplanted or isolated heart. However, the source and molecular identities of these factors remain unknown. Since the efficacy of RPc cardioprotection is critically dependent upon vagal activity and muscarinic mechanisms, we hypothesized that the humoral RPc factor is produced by the internal organ(s), which receive rich parasympathetic innervation. In a rat model of myocardial ischaemia/reperfusion injury we determined the efficacy of limb RPc in establishing cardioprotection after denervation of various visceral organs by sectioning celiac, hepatic, anterior and posterior gastric branches of the vagus nerve. Electrical stimulation was applied to individually sectioned branches to determine whether enhanced vagal input to a particular target area is sufficient to establish cardioprotection. It was found that RPc cardioprotection is abolished in conditions of either total subdiaphragmatic vagotomy, gastric vagotomy or sectioning of the posterior gastric branch. The efficacy of RPc cardioprotection was preserved when hepatic, celiac or anterior gastric vagal branches were cut. In the absence of remote ischaemia/reperfusion, electrical stimulation of the posterior gastric branch reduced infarct size, mimicking the effect of RPc. These data suggest that the circulating factor (or factors) of RPc are produced and released into the systemic circulation by the visceral organ(s) innervated by the posterior gastric branch of the vagus nerve.

Pulse Transit Time as a Predictor of the Efficacy of a Celiac Plexus Block in Patients With Chronic Intractable Abdominal Pain.

OBJECTIVE: There is no well-defined predictor of satisfactory pain relief after celiac plexus block (CPB) at the early stage of treatment. This study evaluated whether measurement of the electrocardiographic R-wave and the arrival time of the pulses at the toe pulse transit time (E-T PTT) can be an early predictor of pain response and success of CPB in patients with chronic intractable visceral pain. METHODS: Twelve patients aged between 20 and 80 years who underwent CPB for treatment of chronic intractable cancer-related abdominal pain were included. A successful CPB was determined as a >50% decrease on the numerical rating scale measured 24 hours after the procedure. The E-T PTT at baseline and at 5, 10, 20, and 30 minutes after the injection of local anesthetic was measured as the time between the R-wave on the electrocardiogram and the peak point of the corresponding plethysmogram wave from the ipsilateral great toe. The change in the E-T PTT that was predictive of a successful CPB was analyzed using receiver operating characteristic curve analysis. RESULTS: A CPB was successful in 9 of 12 cases; the dE-T PTT5/E-T PTT0 of the success group was 6.84%±5.04% versus 0.72%±0.78% in the failure group (P=0.021). The mean E-T PTTx differed significantly between timepoints (F=9.313, P=0.014) and between the success and failure groups (P<0.01). The best value of dE-T PTT5/E-T PTT0 indicating a successful CPB, estimated by receiver operating characteristic curve analysis, was 2.30% (sensitivity 88.9%, specificity 100%). The area under the curve was 96% (95% confidence interval, 85.7%-100%). CONCLUSIONS: Prolongation of E-T PTT at 5 minutes after CPB correlates closely with a significant analgesic effect.

[Electrogastrography in the elderly and effect of hot stupes on the solar plexus].

OBJECTIVES: Constipation affects as many as 26% of elderly men and 34% of elderly women and is a problem that has been related to a diminished quality of life. The aim of this study was to investigate the influence of aging on electrogastrograms (EGGs). On the basis of the EGGs of elderly individuals, the effect of hot stupe application on the epigastrium was also evaluated. METHODS: The first group included 14 healthy, young participants (age, 20-25 years) and the second group comprised 14 healthy, elderly participants (age, 65-76 years). EGGs were obtained for the first 30 min in a sitting position and for the next period (> 150 min) in a supine position. A hot stupe was placed on the epigastrium of each elderly patient 90 min after the postural change. We evaluated EGGs by spectral analysis and nonlinear analysis. RESULTS: On comparing the gastrointestinal electrical activity of the elderly group with that of the young group, the activity in the former revealed an overall decrease. With hot stupe application, translation error in the elderly individuals was significantly larger than that without hot stupe application (p < 0.01). We also observed a gender-specific characteristic, wherein the gastrointestinal motility of the young women was likely only influenced by postural change. Moreover, the translation error in the EGGs of the elderly individuals increased during hot stupe heating. CONCLUSIONS: This increase in the translation error suggests that the electrical synergy between the stomach and intestine could be enhanced by the application of a hot stupe. Our findings also indicated that hot stupe application on the epigastrium was effective for improving gastrointestinal motility in elderly individuals.

From biological gastroenterology to fundamental neurosciences: how studies in gastric emptying have led to the discovery of a new mechanism of neuronal functioning.

Gastric emptying undergoes complex regulation by the nervous system, which organizes in particular the inhibition of duodenum motility after a rise in intra-gastric pressure: the gastro-duodenal inhibitory reflex. It was first shown in mammals that this reflex could be organized by a sympathetic ganglion, the coeliac plexus. The excitation of gastric mechanosensitive fibres leads in this ganglion to the release of a neurotransmitter, which in turn activates ganglionic neurones leading to inhibition of the duodenum contractions. It rapidly became apparent that this reflex presented striking properties since it was organized in the absence of action potentials along the nerve fibres. Then it was shown that the neurotransmitter released in the coeliac plexus was gaseous: nitric oxide (NO). The nature of the mechanism conducting, without action potentials, the excitation along the nerve fibres was recently determined. This mechanism necessitates the integrity of particular areas of the neuronal membrane (the lipid rafts) and the activation in cascade of the following second messenger sequence: ceramide, calcium, NO and guanosine cyclic monophosphate (c-GMP). These results show how studies in biological gastroenterology have led to the rethinking of one of the central dogmas in neuroscience according to which excitation is only conducted along the nerves by the action potential.

Chemotherapy-induced pica and anorexia are reduced by common hepatic branch vagotomy in the rat.

Anticancer agents, such as cisplatin, induce vomiting, nausea, and anorexia. Cisplatin primarily acts on vagal afferents to produce emesis, but little is known about how this drug generates nausea and anorexia. Electrophysiology indicates that cisplatin activates vagal afferents of the common hepatic branch (CHB). Rats lack an emetic response but do ingest kaolin clay (a pica response) when made sick by toxins, and this behavior can be inhibited by antiemetic drugs. It has been postulated that pica may serve as a proxy for emesis in the rat. The goal of this study was to assess the effect of CHB or ventral gastric (Gas) or celiac (Cel) branch vagotomies on pica and anorexia produced by cisplatin in the rat. The effects of apomorphine, a dopamine receptor agonist, which induces emesis via a central mechanism, were also assessed. Cisplatin-induced pica was suppressed by CHB vagotomy (a 61% reduction) but not by Gas and Cel vagotomy. Suppression of daily food intake and body weight following cisplatin treatment was also blunted by CHB ablation but not by Gas or Cel vagotomy. No vagotomy condition exhibited altered apomorphine-induced pica. The results indicate that the CHB, which innervates primarily the duodenum, plays an important role in cisplatin-induced malaise. These data suggest that pica has sensory pathways similar to emetic systems, since a vagotomy condition inhibited cisplatin-induced pica but had no effect on apomorphine-induced pica. This investigation contributes to the delineation of the physiology of pica and neural systems involved in malaise in the nonvomiting rat.

A comparison of two invasive techniques in the management of intractable pain due to inoperable pancreatic cancer: neurolytic celiac plexus block and videothoracoscopic splanchnicectomy.

BACKGROUND AND AIMS: Pancreatic cancer is characterized by a constant deterioration in quality of life, excruciating pain and progressive cachexia. The aim of this study was to compare the effectiveness of two invasive methods of pain treatment in these patients: neurolytic coeliac plexus block (NCPB) and videothoracoscopic splanchnicectomy (VSPL) to a conservatively treated control group concerning pain, quality of life and opiates' consumption. PATIENTS AND METHODS: Fifty nine patients suffering from pain due to inoperable pancreatic cancer were treated invasively with NCPB (N=35) or VSPL (N=24) in two non-randomised, prospective, case-controlled protocols. Intensity of pain (VAS-pain), quality of life (FACIT and QLQ C30) and opioid intake were compared between the groups and to a control group of patients treated conservatively before the procedure and after 2 and 8 weeks of follow-up. The analysis was performed retrospectively using meta-analysis statistics. RESULTS: Both methods of invasive pain treatment resulted in significant reduction of pain (VSPL effect size=11.27, NCPB effect size=7.29) and fatigue (effect sizes, respectively, 1.23 and 3.37). NCPB improved also significantly physical, emotional and social well-being (effect sizes, respectively, 2.37, 4.13 and 7.51) which was not observed after VSPL. No influence on ailments characteristic for the disease was demonstrated. Mean daily opioid consumption was significantly decreased after both procedures. There was no perioperative mortality and no major morbidity. CONCLUSION: Both NCPB and VSPL provide significant reduction of pain and improvement of quality of life in inoperable pancreatic cancer patients. They present rather similar efficacy, but lower invasiveness of NCPB, in combination with its more positive effect on quality of life, pre-disposes it as being the preferred method.

Acid challenge delays gastric pressure adaptation, blocks gastric emptying and stimulates gastric fluid secretion in the rat.

Functional dyspepsia can be associated with impaired gastric relaxation in response to food intake and delayed gastric emptying. In this study, we investigated whether luminal hydrochloric acid (HCl) may reproduce these motor alterations in phenobarbital-anaesthetized rats via activation of extrinsic neural pathways. Intragastric pressure (IGP) changes induced by a 2-mL fluid bolus were recorded with an oesophageal catheter, and gastric emptying was determined via the fluid volume recovered from the stomach 30-min post-bolus. Experiments involving acute nerve transections or pharmacological blockade of nitric oxide synthesis revealed that the initial increase of IGP after a 0.35 mol L(-1) HCl bolus is dampened by duodenogastric and gastrogastric relaxation reflexes depending on vagal and splanchnic pathways as well as nitric oxide. Compared with saline, HCl (0.15-0.5 mol L(-1)) delayed the subsequent decrease (adaptation) of IGP, inhibited gastric emptying and stimulated gastric fluid secretion as seen in stomachs with ligated pylorus. The acid-evoked delay in IGP adaptation and inhibition of gastric emptying involved duodenogastric and duodenopyloric extrinsic nerve reflexes, whereas the gastric fluid secretion was independent of the extrinsic innervation. It is proposed that the gastropyloric motor changes induced by luminal acid challenge have a bearing on the motor disturbances underlying functional dyspepsia.

[Autonomic nervous system and pancreas. (Analysis of the influence of different types of autonomic denervation in glandular regeneration phenomena and the interactions of the exocrine-endocrine-Axis)]. / Sistema nervioso autónomo y páncreas. (Análisis de la influencia de diversos tipos de denervación autonómica en los fenómenos de regeneracón glandular y en las de las interacciones del Eje Endocrino-Exocrino).

The present tests, in male Wistar rats, center around the trophic and functional changes of the pancreatic gland (R G), both exocrine and endocrine, induced by different types of autonomic nervous interruptions. First Group of Tests: Following one year celiac ganglionectomy (CG), nonpancreatectomized (Non-Pt) rats showed, basally, in blood, a drop of glucose (G), without changes of insulin (I). At autopsy, the CG animals showed an increase of the pancreatic we weight, of the total protein, of the RNA but not DNA. In the Pt. 95% rats, superimposing CG triggered, on the one hand, a drop to control values of the raised G blood levels, and on the other, a rise of I Besides, in feces, a rising of chymotrypsin concentration. At autopsy, in the PG, an increase of total protein and of RNA. Second Group of Tests: CG, after 6 months, induced, in blood, both basally and a 2 h glucose tolerance test, significant opposite enzyme activities changes in respect to C. Indeed, as amylase (A) was increased, that of lipase (L) was depressed. When alcohol feeding (AF) was superimposed to CG rats, a reversal of the L values was observed. The latter reached levels significantly higher those of the C. In in-vitro tests, the isolated islets of CG disclosed to release more I to the bath medium than those of the C animals. Third Group of Tests: Analyzing, in conscious animal, the L excretory changes in the basal bile pancreatic secretion (BB-PS) induced by chronic (2 months interruption of the autonomic nervous innervation of the PG, it was found that CG, truncal vagotomy (V), the association of CG + V, peri-Vaterian duodenotomy (PV-D), but not bilateral splachicectomy (Spl), inhibit, significantly the L output. It was also shown that superimosing AF to the V or CG + V animals reverted to C values the I depressed levels. In acute interruptions (24 h) of the autonomic nervous innervation of the PG: CG, V, P. V-D, the depression in the BBPS is highly significant, more than 40%. From these three sets of experiments it is concluded that: Firstly, CG increases the regenerative and functional capacity of both the exocrine pancreas. This is distinctively evident when the secretory mass is reduced like in the Pt. 95% series of animals. CG probably exerts its effects suppressing the releasing of some negative reins: adrenergic, pepdidergic (galanin). Secondly, CG evokes modifications of the normal Islet-pancreon inter-relationships. The rising of A and the drop of L in blood elicited by this type of autonomic nervous interruption probably reflects an increased release of I by the Langerhans islet. Thirdly, CG, the same as V. CG + V and P.V-D, but not Spl, depress the intrapancreatic cholinergic tone. This might by at the basis of the depression of L excretion in the BB-PS. The reversion to C Through the coupling of chronic alcohol intoxication to the autonomic decentralized PG would be a reflection of an increased sensitivity to ethanol of the intrapancreatic ganglionic neurons. The augmented acetylcholine release at the nerve terminal would lead to a high intrapancreatic cholinergic tone that, in the end, might be at the basis of the reversal changes induced in the autonomic decentralized PG by the chronic ethanol intoxication.

Critical evaluation of chemical neurolysis of the sympathetic axis for cancer pain.

BACKGROUND: Patients with pain caused by cancer frequently experience visceral pain. In addition to oral pharmacologic therapy to manage pain, neurolytic blocks of the sympathetic axis are also effective in controlling visceral cancer pain. METHODS: Four types of neurolytic blocks (interpleural phenol, celiac plexus, superior hypogastric plexus, and ganglion impar) used in the treatment of visceral cancer pain are reviewed. RESULTS: Several studies have documented the efficacy of neurolytic blocks in reducing pain intensity and opioid consumption. However, the narrow risk-benefit ratio associated with neurolysis techniques requires knowledge of the implications associated with the different neurolytic blocks to minimize undesirable effects. CONCLUSIONS: Neurolysis of the sympathetic axis has been shown to be an effective and safe approach to treat visceral pain in cancer patients and should be incorporated in the armamentarium of the pain specialist as a useful adjunct to oral pharmacologic therapy.

Responses of celiac and cervical vagal afferents to infusions of lipids in the jejunum or ileum of the rat.

Multiunit celiac and single-unit cervical recordings of vagal afferents were performed before and during infusions of fatty acids, triglycerides, or saline into either the ileum or jejunum of the rat. In multiunit recordings, lipids increased activity of vagal afferents to a greater extent than saline. The greatest increases in vagal afferent activity resulted from infusions of linoleic acid, conjugated linoleic acid, or oleic acid. The triglycerides, corn oil or Intralipid, were less effective than the fatty acids in affecting vagal afferent activity. Ileal pretreatment with the hydrophobic surfactant Pluronic L-81 significantly attenuated the response of celiac vagal afferents to ileal infusion of linoleic acid. Single-unit recordings of cervical vagal afferents supported the multiunit data in showing lipid-induced increased vagal afferent activity in approximately 50% of ileal units sampled and 100% of a limited number of jejunal units sampled. These data demonstrate that free fatty acids can activate ileal and jejunal vagal afferents in the rat, and this effect can be attenuated by pretreatment with a chylomicron inhibitor. These data are consistent with the view that lipid-induced activation of vagal afferents could be a potential substrate for the inhibitory effects of intestinal lipids on gastrointestinal function, food intake, and body weight gain.

Sistema nervioso autónomo y páncreas. (Análise da influencia de diversos tipos de denervación outonómica en los fenómenos de regeneración glandular y en las de las interaciones del eje endocrino-exocrino / Autonomic nervous system and pancreas. (Analysis of the influence of different types of autonomic denervation in glandular regeneration phenomena and the interactions of the exocrine-endocrine-Axis)

The present tests, in male Wistar rsts, center around the trophic and functional changes of the pancreatic gland (R G), both exocrine and endocrine, induced by different types of autonomic nervous interruptions. First Group of Tests: Following one year celiac ganglionectomy (CG), nonpancreatectomized (Non-Pt) rats showed, basally, in blood, adrop of glucose (G), without changes of insulin (I). At autpsy, the CG animals showed an increase of the pancreatic we weight, of the total protein, of the RNA but not DNA. In the Pt. 95 per cent rats, superimposing CG triggered, on the one hand, a drop to control values of the raised G blood levels, and on the other, a rise of I Besides, in feces, a rising of chymotrypsin concentration. At autopsy, in the PG, an increase of total protein and of RNA. Second Group of Tests: CG, after 6 months, induced, in blood, both basally and a 2 h glucose tolerance test, significant opposite enzyme activities changes in respect to C. Indeed, as amylase (A) was increased, that of lipase (L) was depressed. When alcohol feeding (AF) was superimposed to CG rats, a reversal of the L values was observed. The latter reached levels significantly higher those of the C. In in-vitro tests, the isolated islets of CG disclosed to release more I to the bath medium than those of the C animals. Third Group of Tests: Analyzing, in conscious animal, the L excretory changes in the basal bile pancreatic secretion (BB-PS) induced by chronic (2 months interruption of the autonomic nervous innervation of the PG, it was found that CG, truncal vagotomy (V), the association of CG + V, peri-Vaterian duodenotomy (PV-D), but not bilateral splachnicectomy (Spl), inhibit, significantly the L output. It was also shown that superimosing AF to the V or CG + V animals reverted to C values the I depressed levels...

Sistema nervioso autónomo y páncreas. (Análise da influencia de diversos tipos de denervación outonómica en los fenómenos de regeneración glandular y en las de las interaciones del eje endocrino-exocrino / Autonomic nervous system and pancreas. (Analysis of the influence of different types of autonomic denervation in glandular regeneration phenomena and the interactions of the exocrine-endocrine-Axis)

The present tests, in male Wistar rsts, center around the trophic and functional changes of the pancreatic gland (R G), both exocrine and endocrine, induced by different types of autonomic nervous interruptions. First Group of Tests: Following one year celiac ganglionectomy (CG), nonpancreatectomized (Non-Pt) rats showed, basally, in blood, adrop of glucose (G), without changes of insulin (I). At autpsy, the CG animals showed an increase of the pancreatic we weight, of the total protein, of the RNA but not DNA. In the Pt. 95 per cent rats, superimposing CG triggered, on the one hand, a drop to control values of the raised G blood levels, and on the other, a rise of I Besides, in feces, a rising of chymotrypsin concentration. At autopsy, in the PG, an increase of total protein and of RNA. Second Group of Tests: CG, after 6 months, induced, in blood, both basally and a 2 h glucose tolerance test, significant opposite enzyme activities changes in respect to C. Indeed, as amylase (A) was increased, that of lipase (L) was depressed. When alcohol feeding (AF) was superimposed to CG rats, a reversal of the L values was observed. The latter reached levels significantly higher those of the C. In in-vitro tests, the isolated islets of CG disclosed to release more I to the bath medium than those of the C animals. Third Group of Tests: Analyzing, in conscious animal, the L excretory changes in the basal bile pancreatic secretion (BB-PS) induced by chronic (2 months interruption of the autonomic nervous innervation of the PG, it was found that CG, truncal vagotomy (V), the association of CG + V, peri-Vaterian duodenotomy (PV-D), but not bilateral splachnicectomy (Spl), inhibit, significantly the L output. It was also shown that superimosing AF to the V or CG + V animals reverted to C values the I depressed levels...(AU)

Release of nitric oxide within the coeliac plexus is involved in the organization of a gastroduodenal inhibitory reflex in the rabbit.

1. The coeliac plexus can organize a gastroduodenal inhibitory reflex without action potentials. The involvement of the nitric oxide-cGMP pathway in this reflex was investigated in the rabbit on an in vitro preparation of the coeliac plexus connected to the stomach and duodenum. Intraluminal duodenal pressures were measured with water-filled balloons. Gastric distension inhibited duodenal motility, thus characterizing a gastroduodenal inhibitory reflex organized by the coeliac plexus. 2. L-Arginine, superfused at the coeliac plexus level, enhanced this reflex, whereas Nomega-nitro-L-arginine (L-NOARG) or 2-(4-carboxyphenyl)-4,4,5,5 tetramethylimidazoline-1-oxyl-3-oxide (carboxy PTIO) reduced or abolished it. Moreover, diethylamine/nitric oxide complex superfused at the coeliac plexus level inhibited duodenal motility in the absence of gastric distension. 3. The effects of nitric oxide were mediated through the activation of guanylyl cyclase, as 1H-[1,2,4] oxadiazolo [4,3-a] quinoxalin-1-one (ODQ) reduced or abolished the gastroduodenal inhibitory reflex, whereas zaprinast enhanced it. Moreover, 8-bromo-cGMP and cGMP, superfused at the coeliac plexus level, inhibited duodenal motility in the absence of gastric distension. 4. On the other hand, when perfused at the visceral level, L-NOARG, propranolol plus phentolamine, and guanethidine did not affect the reflex. Thus, neither nitric oxide nor noradrenaline could be the transmitters released at the muscular level to induce this reflex. 5. Our study demonstrates that the gastroduodenal inhibitory reflex, which is organized by the coeliac plexus without action potentials, is induced by the release within the plexus of nitric oxide acting on the cGMP pathway. These results provide new insights into the control of digestive motility by the prevertebral ganglia.

Gastroparesis after celiac plexus block.

A 36-yr-old woman with metastatic mucinous cystadenocarcinoma of the pancreas underwent neurolytic celiac plexus block with 100% ethanol and 0.5% bupivacaine for intractable back pain. Several hours after the procedure she developed severe nausea and vomiting, which persisted for days despite cessation of opioid analgesics, and administration of intravenous metoclopramide and ondansetron. Both esophagogastroduodenoscopy and barium examination of the stomach and small intestine showed excess gastric fluid but no evidence of mechanical obstruction. A radionuclide study revealed delayed gastric emptying of solids. Treatment with oral cisapride 10 mg p.o. q.i.d. resulted in considerable symptomatic improvement. We document the first reported case of gastroparesis after celiac plexus block and discuss possible etiological mechanisms.

[The relationship of late slow excitatory potential with 5-hydroxytryptamine and substance P in the guinea-pig celiac ganglion].

The work was carried out to investigate the relationship of non-cholinergic late slow excitatory potential (LS-EPSP) with 5-hydroxytryptamine (5-HT) and substance P (SP) in the neurons of the guinea pig celiac ganglion (CG) using intracellular electrodes in vitro. During repetitive stimulation of the splanchnic nerve (SN), LS-EPSP following a series of action potentials could be recorded in 161 out of 206 neurons (78.2%); Application of 5-HT and SP by superfusion or pressure ejection induced 5-HT depolarization in 102 out of 149 neurons (68.5%) and SP depolarization in 98 out of 188 neurons (52.1%), respectively; Most neurons, from which LS-EPSP could be recorded during stimulation of SN, were sensitive to 5-HT (73/88, 83.0%) and SP (68/114, 59.7%). However, only a small number of neurons not showing LS-EPSP during stimulation of SN were sensitive to 5-HT (10/26, 38.5%, P < 0.0001) and SP (11/36, 30.6%, P < 0.01). The results support the viewpoint that both 5-HT and SP are involved in the formation of LS-EPSP as transmitters; In addition, both effects of 5-HT and SP were examined in 133 neurons. There were 66 of these neurons (49.6%) to be sensitive to both 5-HT and SP, suggesting that there may be some functional relations between 5-HT and SP in the neurons of guinea pig CG.

Suppression of meal size by intestinal nutrients is eliminated by celiac vagal deafferentation.

The arrival of nutrients in the gastrointestinal tract suppresses intake. To specify the neural pathways and receptor locations of this feedback, we examined the effects of intraduodenal infusions of 10 nutrients plus saline on short-term food intake of rats with selective deafferentations of vagal celiac branches. Three response profiles were observed: 1) isotonic saline, 5.6% glycerol, and 3% fructose did not inhibit intake of controls or selectively deafferented animals; 2) 3% glucose, 3% maltose, 3% L-phenylalanine, 12% Isocal, and 1.4% oleic acid suppressed intake of controls, but this inhibition was eliminated by vagal celiac deafferentation; and 3) 3% casein hydrolysate and 24% Isocal suppressed intake of controls and rats with selective vagotomies, although the latter exhibited significantly less suppression. In addition, elimination of celiac afferents chronically reduced meal size (i.e., first 30-min intake) without reducing daily food intake or body weight. Furthermore, D-phenylalanine infusions produced a delayed suppression of food intake in controls (possibly from intraluminal irritation); however, this reduction was eliminated with celiac deafferentation. Overall, this experiment indicates that vagal celiac afferents are critical for preabsorptive detection of some energy-yielding molecules or properties of nutrient solutions (as well as, perhaps, intraluminal inflammation), but not others, which are still detected, although only partially.

Electrophysiological properties of P2X-purinoceptors in rat superior cervical, nodose and guinea-pig coeliac neurones.

1. Whole-cell recordings were made from guinea-pig coeliac, rat nodose and rat superior cervical (SCG) neurones in culture, and currents in response to fast-flow (concentration clamp) application of ATP and other ATP analogues were measured. 2. At a holding potential of -70 mV, ATP evoked inward currents in all neurons. ATP-induced currents reversed at approximately 0 mV and showed strong inward rectification. Halving the external sodium concentration shifted the reversal potential by -15 to -17 mV, while increasing external potassium from 2 to 20 mM produced a 6-10 mV shift in reversal potential. Latency to onset of ATP current was < 1 ms; rise time was concentration dependent with maximum time to peak of 5-20 ms in nodose and coeliac neurones but 80 ms in superior cervical neurones. 3. Threshold concentrations of ATP were 0.1 microM for nodose and coeliac neurones but 10 microM for superior cervical neurones; EC50 values were approximately 3 microM for both nodose and coeliac neurones and 43 microM for superior cervical ganglia. Hill slopes for ATP concentration-response curves were not significantly different from unity in nodose and coeliac neurones whereas the Hill slope in superior cervical neurones was two. 4. 2-MethylthioATP (2-MeSATP) acted as a full agonist in all three neuronal preparations; EC50 values were 0.4, 2.8 and 46 microM for nodose, coeliac and superior cervical neurones, respectively. alpha,beta-Methylene ATP (alpha,beta-MeATP) was a full agonist in nodose and coeliac neurones with EC50 values of 9 and 13 microM, respectively. 5. In superior cervical neurones alpha,beta-MeATP had little or no agonist action but produced a concentration-dependent attenuation of the ATP current. Thus, alpha, beta-MeATP appears to behave as a partial agonist at P2X-purinoceptors in superior cervical neurones. 6. The non-selective purinoceptor antagonists suramin (1-100 microM) and pyridoxal-5'-phosphate (30 microM), as well as the putative P2Y-selective antagonist, Cibacron Blue (30 microM), inhibited all agonist-evoked responses to a similar degree in all three neuronal populations. 7. This study demonstrates that an agonist potency profile of 2-MeSATP > or = ATP > or = alpha,beta-MeATP is characteristic of ligand-gated P2X-purinoceptors in isolated peripheral neurones. We also suggest that the P2X-receptor in superior cervical neurones may represent a distinct subtype of P2X-purinoceptor from that present in nodose and coeliac neurones.