Hyperglycemia Affects Gastric Electrical Rhythm and Nausea During Intraduodenal Triglyceride Infusion

Hyperglycemia slows gastric emptying andincreases the intensity of perception of gastricdistension during fasting and small intestinal nutrientstimulation. In order to examine the possibility thatabnormalities of gastric electrical rhythm may be associatedwith the effects of hyperglycemia, the gastricelectrical rhythm (cutaneous electrogastrogram) and theperception rating scores for upper gastrointestinal sensations (visual analog scale) were examined.Studies were performed during intraduodenal triglycerideinfusion in 10 healthy volunteers under euglycemic andhyperglycemic (15 mmol/liter) conditions. During fasting, hyperglycemia had no effect oneither gastric electrical rhythm or sensation.Intraduodenal triglyceride infusion was associated withan increase in bradygastria (<2.4 cpm) during botheuglycemia (33 9%) and hyperglycemia (36 ± 10%, P< 0.05 vs baseline for each). During intraduodenaltriglyceride infusion, tachygastria (>3.6 cpm) wasmore prevalent during hyperglycemia when compared toeuglycemia (25 ± 10% vs 1 ± 1%, P <0.05) and the perception rating scores for nausea andabdominal discomfort were greater during hyperglycemia(P < 0.05 for both). The intensity of nauseacorrelated with the proportion of time spent in tachygastria (r = 0.64, P < 0.01).These data are consistent with the concept thatpostprandial upper gastrointestinal symptoms in patientswith diabetes mellitus may be modulated by the bloodglucose concentration.     

Effects of Intestinal Electrical Stimulation on Intestinal Dysrhythmia and Symptoms in Dogs

The aim of this study was to investigate the effect of intestinal electrical stimulation on small intestinal dysrhythmia and motion sickness-like symptoms induced by vasopressin. Female dogs chronically implanted with two pairs of electrodes on jejunum serosa were used in a four-session study. Saline and vasopressin were infused in sessions 1 and 2, respectively. Sessions 3 and 4 were the same as session 2, except a long- or short-pulse intestinal electrical stimulation was applied on the proximal pair of electrodes. Intestinal slow waves and motion sickness-like symptoms were recorded in each session. Results were as follows. (1) Vasopressin induced intestinal dysrhythmia, uncoupling of slow waves, and vomiting and motion sickness-like symptoms (P < 0.05, ANOVA). (2) Intestinal electrical stimulation with long pulses, but not short pulses, was capable of preventing vasopressin-induced intestinal dysrhythmia. (3) Intestinal electrical stimulation with short pulses, but not long pulses, prevented vomiting and the motion sickness-like symptoms. It is concluded that vasopressin induces intestinal dysrhythmia. Long-pulse intestinal stimulation normalizes vasopressin-induced intestinal slow-wave abnormalities with no improvement in symptoms. Short-pulse stimulation prevents emetic symptoms induced by vasopressin but has no effect on slow waves. These data suggest different mechanisms involved with different methods of intestinal stimulation.     

Vasoactive intestinal polypeptide-augmented insulin release: actions on ionic fluxes and electrical activity of mouse islets

Summary Vasoactive intestinal polypeptide is a pancreatic neurotransmitter which augments insulin release. To obtain more detailed information on its mode of action on the pancreatic beta cell we studied the effect of vasoactive intestinal polypeptide on⁸⁶Rb⁺ efflux,⁴⁵Ca²⁺ uptake, electrical activity and second messenger systems of isolated mouse islets. Vasoactive intestinal polypeptide enhanced insulin release and⁴⁵Ca²⁺ uptake in a concentration-dependent manner, and was effective at non-stimulatory and stimulatory glucose levels. It increased glucose-induced electrical activity but was without effect on either glucose-mediated changes of⁸⁶Rb⁺ efflux, cAMP or inositol-1,4,5-trisphosphate content. It is suggested that vasoactive intestinal polypeptide augments insulin release by increasing the uptake of Ca²⁺ into the cell by as yet undefined mechanisms.     

Postprandial Response of Jejunal Slow Waves and Mediation via Cholinergic Mechanism

The postprandial characteristics of jejunalmyoelectrical activity and its mediation via cholinergicnerves were investigated in this study. Four pairs ofbipolar electrodes were implanted on the serosa of the proximal jejunum of nine female hounddogs (14-22 kg). In the control session, the recordingof jejunal myoelectrical activity was made for 30 min inthe fasting state and for 90 min after a solid meal (0.45 kg, 838 kcal). The study sessionfollowed the same protocol except that a bolus of 0.25mg/kg atropine was injected intravenously 30 min afterthe meal. Computerized spectral analysis was performed to calculate the frequency, power, andpercentage of 17-22 cycles/min (cpm) slow waves. Aspecial artificial neural network program was applied tocompute the spike bursts superimposed on slow waves. All data were expressed as mean ± SE. Thepostprandial frequency of the jejunal slow waves wassignificantly increased from 18.42 ± 0.28 cpm inthe fasting state to 18.95 ± 0.22, 19.28 ±0.23, and 19.28 ± 0.22 cpm during the first, second, andthird 30-min periods after the meal (all P < 0.03 incomparison with the fasting state). The percentage ofthe slow waves superimposed with spike bursts was increased from 19.33 ± 3.90% at fastingstate to 35.16 ± 2.76%, 32.87 ± 4.06%, and34.88 ± 3.51% during the first, second, and third30-min periods after the meal (all P < 0.03 incomparison with fasting state). Atropine abolished thepostprandial increases in the frequency of slow wavesand the number of spike bursts. No significantpostprandial changes in the power and the percentage of17-22 cpm slow waves were observed. In conclusion,the postprandial response of the jejunal slow wavesafter a solid meal presents as an increase of thefrequency of slow waves and the number of the spikebursts which can be abolished by atropine, and thepostprandial response of the jejunal slow waves is aneural reflex dominantly mediated via vagal cholinergicnerves.     

Effects of bisacodyl on cAMP and prostaglandin E2 contents, (Na+K) ATPase,adenyl cyclase,and phosphodiesterase activities of rat intestine

The hypothesis that bisacodyl induces intestinal fluid accumulation by increasing mucosal PGE₂ content, inhibiting (Na+K) ATPase, and stimulating adenyl cyclase activities was tested in rats. Eighteen hours after its intragastric administration, bisacodyl (5.0 mg/kg body wt) decreased significantly jejunal and colonic (Na+K) ATPase activity: 36.4±1.4 (se) and 28.3±1.4, respectively, as compared to 42.1±1.6 and 37.0±2.9 mol/mg protein/hr in saline-treated rats. Bisacodyl administration increased significantly jejunal and colonic PGE₂ content and stimulated jejunal and colonic adenyl cyclase activity as compared to those in control rats. Jejunal and colonic cAMP content was not significantly increased by bisacodyl. Four hours after its administration, bisacodyl increased intestinal PGE₂ content but failed to stimulate adenyl cyclase activity. Pretreatment with indomethacin prevented the increase in PGE₂ content and the stimulation of adenyl cyclase induced by bisacodyl. Only jejunal phosphodiesterase activity was stimulated by bisacodyl (10 mg/kg body wt). The results reported thus suggest that intestinal inhibition of (Na+K) ATPase activity, increase of mucosal PGE₂ content, and possibly also stimulation of adenyl cyclase activity might contribute to the net water accumulation induced by bisacodyl. It is also suggested that the stimulation of adenyl cyclase activity is mediated by increase in mucosal PGE₂ content.     

Gastric Myoelectrical Activity in Patients with Parkinson's Disease (Evidence of a Primary Gastric Abnormality)

Parkinson's disease patients may experiencevarious gastrointestinal symptoms; however, the exactpathophysiology of these symptoms is not fullyunderstood. Therefore, the aim of this study was toinvestigate the pattern of gastric myoelectrical activityin patients with Parkinson's disease. Eleven patientswith Parkinson's disease and 10 healthy subjectsparticipated in the study. Patients were stratified as receiving dopaminergic therapy (N= 5) and off therapy (N = 6). Gastricmyoelectrical activity was measured by means of surfaceelectrogastrography (EGG) for 30 min before and for 90 min after a standardized meal. The dominantfrequency, postprandial EGG power change, and thepercentage of normal 2-4 cycles/min (cpm) slow-waveactivity in the three groups were calculated andcompared. The mean postprandial EGG power increase in theuntreated patients was smaller than in the treatedpatients (–3.11 ± 1.01 and 1.17 ±1.96 dB; P = 0.072). Moreover, both of these values weresignificantly decreased when compared to the control group(untreated vs control: d–3.11 ± 1.01 vs8.01 ± 1.86 dB; P = 0.04 and treated vs control:1.17 ± 1.96 vs 8.01 ± 1.86 dB; P = 0.02).The percentage of normal 2-4 cpm slow waves in untreated patients wasnot different from the treated patients (82.6 ±6.6% vs 75.8 ± 13.6%, P = NS) or from the controlgroup (88.2 ± 5.4%, P = NS). The dominantfrequency after the meal was similar to that in thefasting state both in the untreated (3.3 ± 0.1 vs3.2 ± 0.2 cpm; P = NS) and treated patients (3.2± 0.1 vs 3.1 ± 0.1 cpm, P = NS), whereasthe dominant frequency significantly increasedpostprandially in the control group (2.88 ± 0.12vs 3.05 ± 0.16; P < 0.05). Abnormalities ingastric myoelectrical activity in untreated Parkinson'sdisease patients reflect direct involvement of thegastrointestinal tract by the primary disease process.EGG can be regarded as a useful diagnostic tool inevaluating gastrointestinal involvement inneurodegenerative diseases.     

Migrating myoelectric complex and jejunal slow-wave propagation after Roux gastrectomy in dogs

Roux-en-Y gastrectomy is associated with a high incidence of symptoms of gastric stasis. Retrograde propagation of jejunal electrical slow waves and spike bursts has been implicated in the Roux Y stasis syndrome. Since the fasted state may persist after feeding, this study examined the extent of retrograde slow-wave propagation in the fasted state, particularly during aboral migration of phase III. Six dogs underwent Roux gastrectomy and placement of bipolar electrodes along the Roux limb. Four normal dogs with electrodes acted as controls. Thirty-five migrating myoelectric complexes were recorded in Roux dogs and 13 in controls. In Roux dogs, the incidences of retrograde propagation of slow waves during the migrating myoelectric complex were phase I 56±13%, phase II 60±12% and phase III 58±14% (not significant). For controls, the incidences were 0%, 0%, and 1%, respectively (P<0.006 versus Roux dogs). In the Roux limb, retrograde propagation of slow waves, and hence spike bursts, occurs even during aboral migration of phase III. This abnormality may contribute to the Roux Y stasis syndrome.An abstract of this work has previously been presented at American Federation for Clinical Research Mid Western Section, October 31, 1990, at Chicago.Supported in part by a grant from the Veterans Administration and from the Department of Surgery, SUNY Health Science Center at Syracuse, Syracuse, New York.     

Stimulation of Intestinal Mucosal Afferent Nerves Increases Superior Mesenteric Artery and Decreases Mesenteric Adipose Tissue Blood Flow

We tested the hypothesis that stimulation of intestinal mucosal afferent nerves produces an increase in superior mesenteric artery (SMA) but a decrease in mesenteric adipose tissue (MAT) blood flow. In anesthetized rats, blood flow in the SMA (pulsed Doppler flowmetry) and MAT (hydrogen gas clearance) was measured simultaneously before and after administration of 0.9% saline, 640 M capsaicin, or 5% dextrose into the intestinal lumen. The changes in the SMA were 3.8 ± 3.0, 15.9 ± 4.0, and 18.8 ± 7.6%; and those in the MAT, 4.7 ± 4.0, –11.5 ± 3.4, and –0.07 ± 3.4% of baseline, respectively. The data indicate that exposure of the intestinal lumen to an afferent nerve stimulant or nutrient induced a dichotomous pattern of blood flow changes, an increase in the SMA and a reduction in MAT. The capsaicin-sensitive afferent nerves may be instrumental in mediating these energy responses.     

Effect of Extrinsic Denervation in a Canine Model of Jejunoileal Autotransplantation on Mechanical and Electrical Activity of Jejunal Circular Smooth Muscle

Little is known about the acute and chroniceffects of the intestinal transplantation on smoothmuscle contractile physiology. Our aim was to determinethe effects of the denervation necessitated byjejunoileal autotransplantation on membrane potential andcontractile activity. Six dogs underwent a model ofjejunoileal autotransplantation that specifically avoidsischemia/reperfusion injury (by maintaining blood flow to the gut during thetransplantation procedure). Strips ofjejunal circular muscle were studied sequentially beforeand 2 and 8 weeks after denervation by recordingmechanical and intracellular electrical activities in vitro. The amplitudeof spontaneous contractions ( ± SD) was increased (P < 0.05) at 2 comparedto 0 weeks (126 ± 19 vs 77 ± 32 g/g; P< 0.05) but markedly decreased at 8 weeks (7 ±2 g/g). Contraction frequency, resting membranepotential, and amplitude of slow waves were unchangedacross these time points. Bethanechol (10^-7-10^-4 M) and substance P (10^-8-10^-6 M) dose-dependently increasedcontractile activity at all time points, but the absolutechange in amplitude was decreased at 8 weeks. Theamplitude of inhibitory junction potentials (IJPs) andduration of inhibition of contractile activity in the presence of cholinergic and adrenergic blockadeincreased at 2 and 8 weeks; off-contraction amplitudewas decreased at 8 weeks (P < 0.05). These effectsmay occur via changes in neurotransmitter release, changes in regulation of membrane receptors, oralteration of characteristics of the membrane thresholdpotential.     

The effects of ischemia on intestinal nerves and electrical slow waves

The effects of prolonged ischemia on the electrical and mechanical activity of the jejunum were studied in acute and chronic preparations in dogs to answer the two questions: (a) Does ischemia alter electrical slow waves of intestinal muscle? (b) Does ischemia cause sufficient damage to intrinsic nerves to account for its effects? Distorted, irregular slow waves with low frequency and poor coupling compared to those in proximal normal segments were recorded in vivo in postischemic segments of chronic preparations. Typical slow waves were not recorded in acute preparations. Although the absence of reflex responses was noted in all postischemic segments, contractions were initiated by drugs acting on nerves. Rhythmic movements were absent in strips isolated from postischemic segments. Severe smooth muscle damage in acute but not in chronic preparations was demonstrated by analyses of ion contents. Jejunal strips from both control and postischemic segments of chronic preparations responded to transmural electrical stimulation. The contractions were decreased by hexamethonium and prevented by atropine or tetrodotoxin. Therefore, prolonged ischemia produced acute damage to smooth muscle and acute and prolonged damage to intrinsic nervous activity, resulting in abolished reflexes and changes in the electrical and mechanical activity of the intestines. However, this technic failed to produce an aganglionic and completely denervated segment.     

Electric Field Stimulation-Induced Guinea Pig Gallbladder Contractions (Role of Calcium Channels in Acetylcholine Release)

Gallbladder motility is modulated by intrinsiccholinergic neurons. The aims of this study were todetermine: (1) the effect of electric field stimulation(EFS) on guinea pig gallbladder smooth muscle, and (2) the role of calcium channels inmediating neurotransmitter release. Gallbladder musclestrips were studied isometrically in vitro. EFS (1-16Hz, 100 V, 0.5-msec pulse width, 30-sec train duration) was used to activate the intrinsic nerves.Exogenous acetylcholine was also used to directlystimulate the smooth muscle. EFS produced afrequency-dependent contractile response that wascompletely abolished by tetrodotoxin. EFS-induced contractions at 16Hz were suppressed by 84 ± 4% with atropine,whereas hexamethonium had no effect. The L-type calciumchannel blocker, nifedipine, reduced EFS contractions by 51 ± 4%, whereas it reduced contractionsto acetylcholine by only 11 ± 5%. The N-typecalcium channel blocker, omega-conotoxin GVIA, reducedEFS-induced contractions by 22 ± 9%, but did notaffect acetylcholine-induced contractions. EFS-induced contractions of theguinea pig gallbladder are primarily mediated byactivation of postganglionic cholinergic neurons. Theacetylcholine release from these cholinergic neurons is regulated by L- and N-type calcium channels.The inhibitory effect of calcium channel blockers on thegallbladder seen in vivo may be in part related toinhibition of acetylcholine release from the intrinsic cholinergic nerves of thegallbladder.     

Impaired Gastric Myoelectrical Activity in Patients with Chronic Renal Failure

Dysmotility and delayed emptying of the stomachhave been reported in patients with chronic renalfailure (CRF). The aim of this study was to investigatewhether gastric myoelectrical activity was impaired in patients with CRF using electrogastrography.The electrogastrogram (EGG) was recorded in 24symptomatic patients with CRF (15 with diabetes) and 12normal subjects. Two 30-min EGG recordings before and after a test meal were analyzed using spectralanalysis methods. It was found that patients with CRFshowed a significantly lower percentage of normal 2-4cpm slow waves in both fasting and fed states in comparison with healthy controls (in fastingstate: 88.9 ± 2.5% vs 67.4 ± 6.6%/63.27.0%, P < 0.01; in fed state: 89.6 ± 1.8% vs64.6 ± 6.2%/62.0 ± 8.3%, P < 0.01;controls vs diabetic patients/nondiabetic patients). Both patient groups showed a significantlyhigher prevalence of the abnormal EGG, which was definedas the percentage of 2-4 cpm slow waves lower than 70%(fasting state: 8% vs 60%/56%, P < 0.01/0.05; fed state: 0% vs 53%/56%, P < 0.005/0.002;controls vs diabetic patients/nondiabetic patients). Nosignificant difference was observed in the regularity ofthe gastric slow waves between the two patient groups. The healthy controls showed a significantincrease in the dominant power and frequency of the EGGafter the test meal. However, this increase was absentin the two patient groups. It was concluded that patients with chronic renal failure haveabnormal gastric myoelectrical activity, includingimpaired regularity of the gastric slow wave and afailed increase in the power of the EGG at 3 cpm.Electrogastrography is an attractive noninvasive method for thestudy of gastric motility in patients with severechronic renal failure.     

Electrical pacing accelerates intestinal transit slowed by fat-induced ileal brake

Previous studies on intestinal electrical stimulation were aimed at achieving a delay in intestinal transit. The aim of this study was to test the hypothesis that the physiological slowing of intestinal transit by the fat-induced ileal brake might be accelerated with intestinal electrical stimulation. This study was performed in five dogs prepared with eight serosal electrodes in the jejunum and two chronic intestinal fistulas located in the duodenum and at the midpoint of the small intestine. To slow transit by triggering the ileal brake, oleate was delivered into the distal half of the gut while buffer was perfused into the proximal half of the gut. Intestinal transit between the fistulas was measured by the recovery of [^99mTc]DTPA. To test for the effect of pacing, transit was compared with vs. without continuous forward electrical stimulation (frequency: 24 cycles/min; pulse duration: 50 msec, pulse amplitude 1–3 mA). Electrical stimulation completely entrained intestinal pacesetter potentials as measured from the seven recording electrodes distal to the pacing electrode. A substantial and significant increase in intestinal transit was observed with intestinal electrical stimulation with the percentage of marker recovery increasing from 19.2 ± 9.3% to 84.6 ± 11.3% (P < 0.01). In conclusion, intestinal electrical stimulation accelerates intestinal transit slowed by ileal brake.     

Entrainment of Segmental Small Intestinal Slow Waves with Electrical Stimulation in Dogs

The aim of this study was to derive effective pacing parameters for the entrainment of segmental intestinal myoelectrical activity. The study was performed in 12 dogs. Four pairs of electrodes were implanted on the serosa of the jejunum. Electrical stimulation of the small intestine was performed via the most proximal pair. For the slow waves within a distance of 5 cm, a complete entrainment was achieved with a pacing frequency of 1.1 times the intrinsic frequency (IF), a pulse width of 140 msec, and an amplitude of 4 mA. The time required for the entrainment was 25.6 ± 2.7 sec. The maximum driven frequency was 1.38 ± 0.03 IF. The percentage of the entrainment at this frequency was 44.0 ± 3.9%. The data indicate that pacing is able to completely entrain segmental intestinal myoelectrical activity, suggesting that normalization of intestinal myoelectrical dysrhythmia is feasible with pacing.     

Gastroduodenal electrical activity in turkeys

Bipolar Ag/AgCl electrodes were implanted in the stomach and duodenum of 21 turkeys to study electrical activity in those organs. Intraluminal pressure changes were also monitored. For comparative purposes, electric slow waves were recorded from the ileum of one dog. Slow waves were not observed in the recordings from the stomach of turkeys. Although slow waves were recorded from the duodenum of turkeys, the waves were observed to wax and wane and were possibly not the major regulators of duodenal contractile activity. Several bursts of action potentials and several contractions usually occurred in the duodenum during one slow-wave cycle. Duodenal motility appeared to be totally coordinated with the gastric cycle. Impulses conducted over intrinsic nerves from a gastric pacemaker (15) were proposed as a possible mechanism for initiating and coordinating gastroduodenal motor activity.     

Impaired Postprandial Gastric Myoelectrical Activity in Chinese Patients with Nonulcer Dyspepsia

Using a homemade electrogastrography (EGG) system, we studied the characteristics of the myoelectrical rhythm in Chinese patients with nonulcer dyspepsia (NUD). Based on short-term Fourier transformation, recorded slow waves could be automatically analyzed to obtain the following parameters: dominant frequency/power, percent of normal frequency (2–4 cpm), power ratio, etc. EGG parameters, Helicobacter pylori status, histological examination of gastric mucosa, and dyspeptic symptoms were recorded in 27 NUD patients. Compared to 32 healthy controls, the Chinese NUD patients had abnormal postprandial EGG parameters including a lower percentage of regular 2–4 cpm slow waves (70.10 ± 2.97% vs 79.08 ± 2.95%, P < 0.05), a lower level of increment of dominant power (0.62, ± 0.91 vs 3.76 ± 0.58 dB, P < 0.05), lower power ratio (1.42 ± 0.28 vs 2.79 ± 0.39, P < 0.05) and a higher instability coefficient (0.36 ± 0.03 vs 0.26 ± 0.03, P < 0.05). However, Helicobacter pylori infection and its associated gastritis did not influence any EGG parameters in NUD patients. Six main dyspeptic symptoms and total symptom score had no correlation with any EGG parameters. In conclusion, Chinese NUD patients may have abnormal postprandial stomach myoelectrical activity, but these EGG abnormalities are not a direct result of Helicobacter pylori infection and its related gastritis and do not contribution to the dyspeptic symptoms.     

Effect of dopamine on electrical activity of isolated stomach muscle in cats

The effect of dopamine on electrical activity (gastric slow wave) of the stomach was studied in isolated stomach muscle strips of 145 cats. The gastric slow wave was recorded by four monopolar electrodes (Ag-AgCl) in Krebs-Ringer solution (pH 7.4, temperature 36±0.5° C) bubbled with 5% CO₂ in O₂. Dopamine induced concentration-dependent alterations in frequency and propagation of slow waves. Development of irregular propagation was significantly suppressed by domperidone pretreatment. The variation of dopamine-induced slow-wave frequency was significantly inhibited by domperidone and phentolamine but not by propranolol, hexamethonium, and tetrodotoxin. The study indicates that a dopamine receptor exists in the stomach and plays a role in the genesis of gastric electrical abnormality.This study was supported by The Catholic Medical Center Research Fund and in part by Research Grant of The Ministry of Education, Republic of Korea.     

Triggering sleep slow waves by transcranial magnetic stimulation

During much of sleep, cortical neurons undergo near-synchronous slow oscillation cycles in membrane potential, which give rise to the largest spontaneous waves observed in the normal electroencephalogram (EEG). Slow oscillations underlie characteristic features of the sleep EEG, such as slow waves and spindles. Here we show that, in sleeping subjects, slow waves and spindles can be triggered noninvasively and reliably by transcranial magnetic stimulation (TMS). With appropriate stimulation parameters, each TMS pulse at <1 Hz evokes an individual, high-amplitude slow wave that originates under the coil and spreads over the cortex. TMS triggering of slow waves reveals intrinsic bistability in thalamocortical networks during non-rapid eye movement sleep. Moreover, evoked slow waves lead to a deepening of sleep and to an increase in EEG slow-wave activity (0.5-4.5 Hz), which is thought to play a role in brain restoration and memory consolidation.     

Myoelectric and contractile effects of motilin on dog small intestinein vivo

The effects of the close intraarterial administration of motilin on intestinal myoelectric and contractile activities were examined in 37 dogs. After anesthetization or decerebration, a segment of proximal jejunum was instrumented serosally with electrodes and stain gauges. A mesenteric artery supplying a short length of this segment was cannulated for the injection of motilin and other agents. Motilin (0.03–0.3 g) caused: (1) a series (1–5 min) of phasic contractions and electrical response activity (ERA) bursts locally; (2) a short (15–60 sec) series of phasic contractions and ERA bursts aborally followed by relaxation; and (3) a series of phasic contractions and ERA bursts whose onset migrated 3.7±1.0 cm orally. The length of orad response increased to 6.6±1.9 cm in the decerebrate dogs (P<0.01). No other tested agent, including serotonin, bethanechol, morphine, dopamine, substance P, neurotensin, somatostatin, vasoactive intestinal peptide, bombesin, pentagastrin, cholecystokinin octapeptide, prostaglandin F₂ or leucine-enkephalin, cuased similar responses. All motilin responses were mediated by neural pathways consisting of both nicotinic and muscarinic receptors. The similarity of responses and mechanisms of action of the motilin-activated contractile response with the intrinsic mucosal reflex suggested that motilin may mediate this reflex.This work was supported in part by VA grant 7722-01P.     

Action and localization of vasoactive intestinal peptide in the coronary circulation: evidence for nonadrenergic, noncholinergic coronary regulation

Vasoactive intestinal polypeptide, a neurotransmitter peptide detected in animal and human hearts, has been found in nerves of coronary arteries. To determine the amount and distribution of vasoactive intestinal polypeptide in the large coronary vessels and its possible participation in coronary vasoregulation, two groups of animals were studied. In the first group, 11 anesthetized dogs were sacrificed to collect three (1 cm) segments along the circumflex and left anterior descending coronary arteries. These segments represented proximal (I), middle (II) and distal (III) portions of the two arteries. Concentrations (ng/g) of vasoactive intestinal polypeptide-like immunoreactive substance were determined by radioimmunoassay. Vasoactive intestinal polypeptide-like immunoreactivity was present in the left anterior descending (I = 7.28 +/- 1.65, II = 3.74 +/- 0.57, III = 2.29 +/- 0.53) and circumflex (I = 4.16 +/- 1.52, II = 4.58 +/- 1.13, III = 4.00 +/- 0.81) coronary arteries. The difference in vasoactive intestinal polypeptide-like immunoreactivity among epicardial segments of the anterior descending artery was significant, but there was no significant difference among segments of the circumflex coronary artery. In the second group (eight closed chest anesthetized dogs), the effects of vasoactive intestinal polypeptide intracoronary infusion on epicardial coronary constriction were examined at rest and with the artery constricted by serotonin. Left anterior descending (segments I, II and III) artery responses (% area change) to vasoactive intestinal polypeptide and vasoactive intestinal polypeptide plus serotonin were examined using quantitative coronary angiography. Vasoactive intestinal polypeptide infusion resulted in significant vasodilation in all the segments (I, II and III) of the left anterior descending artery.(ABSTRACT TRUNCATED AT 250 WORDS)