Change of the involvement of 5-HT3 receptor in the gastric motor stimulating actions of KW-5139 (Leu13-motilin acetate) in the recovered and post-operative periods in dogs

We have previously reported that KW-5139, a motilin analogue, evokes gastrointestinal motor stimulating action in the post-operative period as well as in the recovered period of conscious dogs. In this report, we compared the mechanisms of the KW-5139-induced contractions in the post-operative period with those in the recovered period using beagle dogs implanted force transducers in the gastric antrum, duodenum, jejunum, ileum and colon. In addition, we also examined the mechanisms of the prostaglandin F2alpha-induced contractions in both periods. The gastric contractions evoked by KW-5139 (0.5 microg kg(-1), i.v.) were inhibited by the pretreatment of ondansetron (0.1 mg kg(-1), i.v.), a 5-HT3 receptor antagonist, in the recovered period, but were not affected in the post-operative period even by higher doses of ondansetron (0.3-1 mg kg(-1), i.v.). The KW-5139-induced contractions in the small and large intestine were not inhibited by ondansetron in the both periods. The contractions evoked by KW-5139 (0.5 microg kg(-1), i.v.) in the gastric antrum, duodenum, jejunum and colon were significantly inhibited by the pretreatment with atropine (0.05 mg kg(-1), i.v.), a muscarinic receptor antagonist, in the recovered period as same extent as in the post-operative period. The contractions evoked by prostaglandin F2alpha (50 microg kg(-1), i.v.) in the any recording sites were not affected by the pretreatment with ondansetron (0.1 mg kg(-1), i.v.) in the recovered period. On the other hand, atropine (0.05 mg kg(-1), i.v.) tended to inhibit the gastric and colonic contractions. These effects of ondansetron and atropine on the prostaglandin F2alpha-induced contractions were not different between in the post-operative and recovered periods. The present results indicate that 5-HT3 receptors are involved in the KW-5139-induced motor stimulating action in the recovered period but not in the post-operative period. The mechanisms of the alteration were discussed.     

The effect of difluorodichloromethane (FC 12) on isolated rat and rabbit heart]

We have tried to determine if dichlorodifluoromethane (F.C. 12) might have an effect in vitro on the isolated rat and rabbit hearts. The direct action of F.C. 12 on the heart in vitro is similar in both rats and rabbits. It occurs at doses such as 20 +/- 10 mug/ml (rat) and 35 +/- 5 mug/ml (rabbit). F.C. 12 depresses the strength of the myocardial contractions; the effect is reversible at low concentration (less than 60 mug/ml) but irreversible at high concentration (greater than or equal to 120 mug/ml). It also causes a slight bradycardia, but no significant effect on the basal tonus. At high concentration, F.C. 12 may produce arrhythmia : this action occurs more readily in the rat heart than in the rabbit heart.     

Bombesin-induced changes in membrane potential-dependent phasic contractions of cat gastric muscle

Electrical and contractile activities of smooth muscle strips isolated from the circular muscle layer of cat gastric antrum were studied using the sucrose gap technique. Bombesin (10(-8) mol/l) depolarized the gastric muscle; this was accompanied by an increase in the strip tone, in the plateau action potential frequency and in both the frequency and the amplitude of the spike potentials as well as by a shortening of the plateau action potential duration. Both the frequency and the amplitude of the phasic contractions increased thereafter. The changes in the frequency of the plateau action potentials and contractions were not influenced either by antagonists of cholinergic and adrenergic receptors or by TTX. In the presence of the Ca antagonists D600 (10(-6) mol/l) and nifedipine (10(-7) mol/l) or in Ca-free medium containing EGTA the effect of bombesin on the frequency of the plateau action potentials and phasic contractions remained unchanged; however, spike potentials were not observed and no increase in the amplitude of phasic contractions occurred. UV-light inactivation of nifedipine restored the typical bombesin effect on the electrical and contractile activities of the gastric smooth muscle. The present data suggest that the effect of bombesin on the frequency of both plateau action potentials and phasic contractions is not linked with Ca2+ influx.     

Multiple transmitter neurons in Tritonia. III. Modulation of central pattern generator controlling feeding

Feeding behavior in the gastropod mollusc Tritonia diomedea is controlled by a central pattern generator (CPG) in the buccal ganglia. The medially located, large dorsal white cells (B11) have been shown to contain two small cardioactive peptides (SCPs). A smaller nearby neuron (B12) also appears to contain the SCPs. B11's have also been shown to contain acetylcholine (ACh), whereas B12's do not. We have shown earlier that intracellular stimulation of B11's drives contractions of the foregut. Here we show that intracellular electrical stimulation of B11's also elicits excitation of neurons B5 and stimulates the patterned motor output of the CPG. We showed earlier that B12's also stimulate contractions in the foregut, but they are in the opposite direction from those elicited by B11. We show here that electrical stimulation of B12's inhibits the output of the CPG. We showed earlier that superfusion of the isolated gut with SCPB enhances peristalsis, and here we report that superfusion of the buccal ganglion with SCPB elicits enhanced coordinated motor output from the CPG. The peptide has two effects on the bursting output of motor neurons. It produces an increase in (1) the rate of bursting and (2) the spike frequency during each burst. On the other hand, we reported earlier that ACh applied directly to isolated foregut inhibits ongoing peristalsis. Here we demonstrate that ACh superfusion of the buccal ganglion also inhibits the CPG output. Our evidence supports the view that in addition to stimulating foregut contractility, B11's modulate the output of the swallowing CPG by releasing a peptide from central terminals. We suggest roles for B11, B12, the SCPs, and ACh in controlling both central and peripheral aspects of feeding behavior.     

Bradykinin receptors in intestinal smooth muscles and their post-receptor events related to calcium

The effects of trifluoperazine and verapamil on bradykinin- and des-Arg(9)-bradykinin induced responses of isolated rat duodenum and guinea-pig ileum were investigated to elucidate post-bradykinin receptor events. Verapamil and trifluoperazine inhibited bradykinin induced relaxations and contractions and des-Arg(9)- bradykinin induced contractions in rat duodenum. Bradykinin induced contractions of ileum were also inhibited by trifluoperazine and. verapamil. Since non-competitive affinity constants of trifluoperazine and verapamil for the relaxant responses to bradykinin in duodenum and for the contractile responses to bradykinin in ileum are different, post-bradykinin receptor events related to calcium may be different in ileum and duodenum. In addition, affinity constants of bradykinin in guinea-pig ileum and rat duodenum are also disparate suggesting the presence of different types of bradykinin B(2) receptors in these two organs.     

Mechanisms underlying nutrient-induced segmentation in isolated guinea pig small intestine

Mechanisms underlying nutrient-induced segmentation within the gut are not well understood. We have shown that decanoic acid and some amino acids induce neurally dependent segmentation in guinea pig small intestine in vitro. This study examined the neural mechanisms underlying segmentation in the circular muscle and whether the timing of segmentation contractions also depends on slow waves. Decanoic acid (1 mM) was infused into the lumen of guinea pig duodenum and jejunum. Video imaging was used to monitor intestinal diameter as a function of both longitudinal position and time. Circular muscle electrical activity was recorded by using suction electrodes. Recordings from sites of segmenting contractions showed they are always associated with excitatory junction potentials leading to action potentials. Recordings from sites oral and anal to segmenting contractions revealed inhibitory junction potentials that were time locked to those contractions. Slow waves were never observed underlying segmenting contractions. In paralyzed preparations, intracellular recording revealed that slow-wave frequency was highly consistent at 19.5 (SD 1.4) cycles per minute (c/min) in duodenum and 16.6 (SD 1.1) c/min in jejunum. By contrast, the frequencies of segmenting contractions varied widely (duodenum: 3.6-28.8 c/min, median 10.8 c/min; jejunum: 3.0-27.0 c/min, median 7.8 c/min) and sometimes exceeded slow-wave frequencies for that region. Thus nutrient-induced segmentation contractions in guinea pig small intestine do not depend on slow-wave activity. Rather they result from a neural circuit producing rhythmic localized activity in excitatory motor neurons, while simultaneously activating surrounding inhibitory motor neurons.     

5-Hydroxytryptophan modulates postprandial motor patterns of canine proximal small intestine

The aim of the study was to clarify whether 5-hydroxytryptophan (5-HTP) stimulates the postprandial motor pattern of the duodenum in a similar way as that of the adjacent jejunal segment in dogs. Computerized analysis of motor patterns recorded by closely spaced strain gauges focused on the temporal and spatial distribution of the contractions. Results indicate that 5-HTP increased the incidence and the length of the spread of contraction waves after both an acaloric and a nutrient meal in the duodenum as well as in the adjacent jejunal segment. Effects were more pronounced after the nutrient than after the acaloric meal. After the nutrient meal, but not after the acaloric meal, 5-HTP additionally enhanced the number of both duodenal and jejunal contractions per minute and increased the force of duodenal contractions. The acaloric meal induced significant differences in the motor patterns between the duodenum and the adjacent jejunum. 5-HTP abolished these differences owing to a relatively stronger stimulation of duodenal motility. 5-HTP did not affect gastric emptying of both meals. We conclude (i) that 5-HTP is a potent stimulator of propagated contractions both in the duodenum and the adjacent jejunal segment and (ii) that intestinal motor patterns can be regulated independently of gastric emptying.     

Clonazepam and diltiazem both inhibit sodium-calcium exchange of mitochondria, but only diltiazem inhibits the slow action potentials of cardiac muscles

Clonazepam, up to concentrations of 5 x 10(-5) M produced only 15% inhibition of contraction without effecting isoproterenol-induced slow action potentials (APs) of guinea pig papillary muscles. On the other hand, 10(-6) M diltiazem completely inhibited both slow APs and contractions. Both clonazepam and diltiazem inhibited Na+-induced Ca2+ release from isolated mitochondria. The half-maximum effect of clonazepam and diltiazem occurred at 7 and 8 x 10(-6) M respectively. The results suggest that clonazepam more specifically inhibits the Na+-induced Ca2+ release process of mitochondria.     

Spantide II, a novel tachykinin antagonist having high potency and low histamine-releasing effect.

Two undecapeptide substance P (SP) analogues, Spantide I and Spantide II, were tested for their capacity to block the contractile effect of SP on the guinea pig isolated taenia coli and the contractile effect of electrical stimulation of the rabbit isolated (and atropinized) iris sphincter, and for their capacity to mobilize histamine from rat isolated peritoneal mast cells. Spantide I and Spantide II have one feature in common, namely D-tryptophan in positions 7 and 9. Spantide I: D-Arg, Pro2, Lys3, Pro4, Gln5, Gln6, D-Trp7, Phe8, D-Trp9, Leu10, Leu11-NH2. Spantide II: D-NicLys1, Pro2, 3-Pal3, Pro4, D-Cl2Phe5, Asn6, D-Trp7, Phe8, D-Trp9, Leu10, Nle11-NH2. Both Spantide I and II were found to be competitive antagonists to SP on the taenia coli and to be capable of blocking the electrically induced non-cholinergic contraction of the iris sphincter. Spantide II had higher pA2 value (taenia coli) than Spantide I, 7.7 versus 7.0, and higher pIC50 value (blockade of tachykinin-mediated neurotransmission in iris sphincter), 6.0 versus 5.1. Both Spantide I and II mobilized histamine from rat peritoneal mast cells but Spantide II was less effective. Spantide I and II were tested for antagonistic specificity. Both blocked contractions of the taenia induced by SP and neurokinin A. In the concentration used, Spantide II in addition blocked the response to neurokinin B. The contractions induced by carbachol, 5-hydroxytryptamine, histamine and prostaglandins (F2 alpha and E1) were not affected; the contractile response to bombesin was inhibited by Spantide I but not by Spantide II.     

Nociceptin receptor activation inhibits tachykinergic non adrenergic non cholinergic contraction of guinea pig isolated bronchus

We studied the action of nociceptin (NC) on the atropine-resistant contractions of the guinea pig isolated bronchus evoked by the electrical field stimulation (EFS), an effect that is mediated by the activation of excitatory non adrenergic-non cholinergic (eNANC) nerves and the subsequent release of tachykinins. The functional site by which NC acts in this preparation was investigated using few different NC receptor agonists and the newly discovered NC receptor antagonist, [Phe1psi(CH2-NH)Gly2]NC(1-13)NH2 ([F/G]NC(1-13)NH2). NC inhibited in a concentration dependent manner (pEC50 7.14; Em - 87 +/- 3% of control values) EFS induced contractions. NC effect was mimicked by the NC analogues, NCNH2 and NC(1-13)NH2, but not by NC(1-9)NH2. NC (1 microM) did not affect the contractile effects of exogenously applied neurokinin A (1 microM). [F/G]NC(1-13)NH2 (10 microM) completely prevented the inhibition induced by NC (1 microM), whereas naloxone (1 microM) was found inactive. Both naloxone and ([F/G]NC(1-13)NH2 were per se inactive on basal resting tone as well as on the electrically induced contractions. The present findings show that NC inhibits the atropine-resistant EFS-induced contraction in the guinea pig bronchus by inhibiting eNANC nerves, and suggest the presence of NC receptors, distinct from opioid receptors, on the nerves of the guinea pig bronchus.     

Effects of external calcium, magnesium, and temperature on spontaneous contractions of pregnant human myometrium

Spontaneous isometric contractions of small isolated segments from the isthmic region of pregnant human myometrium were recorded to clarify the characteristics of and influences of experimental conditions on contractions. There is a spontaneous periodicity in membrane activity of human myometrium, and contractions evoked with a sustained electric stimulus were affected by spontaneous rhythmic contractions. The frequency of contractions increased markedly, but their duration decreased when temperature of the bathing fluid was increased from 26 degrees C to 39 degrees C. Both excess (7 mM) and low (0.5 mM) calcium levels suppressed the generation of spontaneous contraction. Frequency and half-duration gradually decreased when external magnesium was increased from 0 mM to 3.6 mM. These results indicate that the pattern of contraction depends on the frequency of and intervals between each action potential, and that spontaneous contractility-particularly its frequency-is extremely sensitive to external temperature and ionic conditions.     

Effect of fasting on small intestinal antiperistalsis in the Nicholas turkey (Meleagris gallopavo)

Small intestinal refluxes (SIRs) were monitored in the gastrointestinal tract of Nicholas turkeys via implanted strain gage transducers and radiographic observations. It was determined that reflux of ingesta from the small intestine into the gizzard was a result of a single antiperistaltic contraction. Radiographic observation indicated that the antiperistaltic contraction originated in the ileum 88% of the time and the duodenum 12% of the time. Each antiperistaltic contraction was preceded by a single peristaltic contraction. No gastric contractions occurred during SIRs. Fasting for 12 to 24 hr significantly increased the frequency of occurrence of SIRs in the Nicholas turkey (P < 0.0001) but had no significant effect on the velocity of the peristaltic and antiperistaltic contractions or on recovery time to pre-SIR gastric contractile frequency. The pooled mean velocity of peristaltic contractions was determined to be 10.55 +/- 3.68 cm/sec, and that of antiperistaltic contractions was determined to be 12.12 +/- 3.69 cm/sec. The pooled mean recovery time to pre-SIR gastric contraction frequency was 28.31 +/- 8.25 sec. It has been suggested that the SIR may be a mechanism of maximizing nutrient utilization by the turkey.     

Possible role of Na(+)-Ca2+ exchange in the regulation of contractility in isolated adult ventricular myocytes from rat and guinea pig

Action potentials and developed contractions of externally unloaded single ventricular myocytes isolated from adult rat and guinea pig hearts were recorded by means of an optical system for recording contractile activity during regular stimulation by microelectrodes. Under control conditions, the shortenings (twitches) in the rat myocytes were fully inhibited by 0.1 microM ryanodine, but they were rather insensitive to the Ca2+ blocker 0.2-0.5 microM nifedipine. In contrast, the contractions of the isolated guinea pig ventricular myocytes were greatly suppressed by 0.2-0.5 microM nifedipine (to less than 30%), while they were only slightly reduced by 1 microM ryanodine. When the Na+ gradient was decreased by reducing [Na]o or by elevating [Na]i in the presence of veratridine, the twitch contractions were increased in both species. The effect of reduced [Na]o on twitch contractions was not affected by ryanodine in either type of myocytes, while nifedipine still fully abolished the twitches in the guinea pig cells, indicating a strong dependence of guinea pig contractions on Ca2+ influx. On the other hand, the effect of a reduced Na gradient by veratridine was more complex; the usual twitch (phasic component) was increased and it was followed by a second (tonic) component which relaxed only after the repolarization of the action potential. While the phasic component was decreased by nifedipine and ryanodine in the usual way (as in the controls), the sustained contractions (lasting up to several seconds) were ryanodine and nifedipine insensitive. Furthermore, the cardiomyocytes of both species exposed to strontium in place of external calcium still exhibited all the effects observed when reducing the Na+ gradient.(ABSTRACT TRUNCATED AT 250 WORDS)     

Mechanism of inhibitory action of peptide YY on cholecystokinin-induced contractions of isolated dog ileum

In isolated canine ileal longitudinal muscle preparations, cholecystokinin-octapeptide (CCK-8) produced a concentration-dependent contraction, which was suppressed by peptide YY (PYY) and was abolished by tetrodotoxin and atropine. PYY was approximately 2200-times as potent as CR1505, a CCK-receptor antagonist. PYY opposed the action of CCK-8 to a greater extent than that of nicotine and transmural electrical stimulation. Acetylcholine-induced contractions were not influenced by PYY. It seems likely that the CCK-8-induced ileal muscle contraction is associated with an activation of CCK receptors in cholinergic nerves, which generates nerve action potentials and releases acetylcholine, whereas CCK-8 acts on CCK receptors in gallbladder smooth muscle, producing contractions. It may be concluded that PYY inhibits the action of CCK-8 on ileal muscle strips, by inhibiting the release of acetylcholine from cholinergic nerve terminals. On the other hand, in the gallbladder, PYY does not appear to block cholinergic nerve function.     

Functional and immunocytochemical evidence that galanin is a physiological regulator of human jejunal motility.

The neuropeptide galanin has species-dependent effects on intestinal motility. It has a contractile effect on rat jejunal muscle while it relaxes guinea-pig ileum by inhibiting cholinergic transmission. Its effect on human gut motility has been unknown. Extensive work led to the discovery of selective galanin analogues such as M15 [galanin(1-12)-Pro-substance-P(5-11)], M35 [galanin(1-12)-Pro-bradykinin(2-9)-amide] that competitively inhibit various actions of galanin in the central nervous system. The present study was designed to examine the effect of galanin, M15 and M35 on longitudinal jejunal smooth muscle strips isolated from humans and rats, and to localize galanin-immunoreactivity in human jejunum. Galanin and ACh were equally effective in stimulating contractions of the isolated jejunal muscle: sigmoid curve fitting showed that maximal contractile response to galanin and ACh were 25.7+/-11.1 mN and 23.7+/-9.7 in humans, while 8.0+/-0.6 and 8.1+/-0.3 mN in rats, respectively. These effects of galanin were not inhibited by either atropine (5 x 10(-6) M) or tetrodotoxin (3 x 10(-6) M). The potency of galanin inducing the contractile actions were similar in humans and rats. Interestingly, neither M15 nor M35 (up to 10(-7) M) were able to inhibit the responses of the smooth muscle to galanin. However, both putative galanin receptor antagonists showed agonist effects in our experimental models. In accordance with the functional studies, both the longitudinal and the circular muscle layers were abundant in nerve fibers and varicosities showing galanin immunoreactivity. Our data suggest that galanin is a potent physiological regulator of jejunal contractions in humans. Its action on the jejunum, however, is mediated by galanin receptors that are different from those located in the central nervous system.     

Histamine H1 receptors and prostaglandin-histamine interactions modulating contractility of rabbit and rat testicular capsules in vitro

The stimulatory effect of histamine on rabbit and rat testicular capsule was blocked by the H1 blocker, diphenhydramine, but not by the H2 blocker, cimetidine, suggesting the presence of H1 histamine receptors in both rabbit and rat testicular capsules. In the rabbit, both anti-prostaglandin F (PGF) and anti-prostaglandin E (PGE) effaced spontaneous autorhythmic contractions. They markedly inhibited PGF 2 alpha, PGE1 and histamine-stimulated contractions of the rabbit testicular capsule. In the rat, anti-PGF or anti-PGE had no inhibitory effects on the capsular tone, but they both inhibited the stimulatory effects of histamine. These data suggest that the action of histamine on the rabbit and rat testicular capsules could be due partly to a secondary release of the PG's, PGE2 and PGF2 alpha.     

Contractile action of heat-labile toxin of Bordetella parapertussis on aortic smooth muscles of pigs

Using both vascular smooth muscle strips (VSMS) and cultured cells (VSMC) from aortas of pigs, the contractile action of Bordetella heat-labile toxin (HLT) purified from B. parapertussis was studied in an attempt to elucidate the mechanisms of its action. HLT induced contractions in VSMC in parallel with the increase of Ca2+-influx. The HLT-induced Ca2+-influx and contraction were not influenced by verapamil or diltiazem, though a certain extension of the lag period was seen. The contractile action of HLT on VSMS and VSMC was not influenced either by diltiazem or quinacrine; that on VSMC was not influenced by prednisolone, indomethacin, aspirin, CV-3988, FPL-55712, ruthenium red, or TEAC. On VSMS, prednisolone caused the extension of lag period following HLT exposure. The action of HLT on VSMS was inhibited by TMB-8, whereas that on VSMC was not though the extension of lag period was seen. The HLT-induced contraction in both VSMS and VSMC was completely inhibited by H-7. The contraction in VSMS, but not in VSMC, was inhibited by H-8. HLT did not induce specific activation of the protein kinases in VSMC. The addition of cGMP or cAMP brought about relaxation in the HLT-exposed VSMS contracting in maximum. HLT caused a significant increase in permeability of VSMC membrane to trypan blue, accompanied with contraction. Both HLT-induced contraction and increase in permeability were inhibited by dextran of M.W. 8,000, but not of M.W. 5,000. These results suggested that HLT acted on vascular smooth muscle cells by damaging the membrane permeability, but not by disturbing the known cascades or systems for physiological contractions, resulting in the increase in Ca2+-influx and then contractions.     

Effects of dried bonito (katsuobushi) and captopril, an angiotensin I-converting enzyme inhibitor, on rat isolated aorta: a possible mechanism of antihypertensive action

In order to elucidate the mechanism of the antihypertensive action of dried bonito (katsuobushi), we compared the effects of dried bonito extracts with those of captopril, an angiotensin I-converting enzyme (ACE) inhibitor, on aorta preparations isolated from rats. Dried bonito extracts (3 x 10(-4) to 3 x 10(-3) g/ml) more potently relaxed contractions induced by norepinephrine (10(-7) M) than contractions induced by KCl (55.9 mM). Dried bonito extracts (3 x 10(-3) g/ml) slightly inhibited 10(-7) M angiotensin I-induced contractions. In contrast, captopril (10(-8) to 10(-7) M) did not affect 10(-7) M norepinephrine- or 55.9 mM KCl-induced contractions, but a higher concentration of captopril (10(-6) M) very slightly relaxed it. Captopril (10(-8) to 10(-6) M) markedly inhibited 10(-7) M angiotensin I-induced contractions in a concentration-dependent manner. These results suggest that antihypertensive mechanism of action induced by dried bonito involves direct action on vascular smooth muscle in addition to ACE-inhibitory activity.     

Cardiac arrhythmia in the rabbit under the effect of adrenaline and difluorodichloromethane (FC12)]

Inhalation of gas mixtures containing different concentrations of FC12 by anesthetized and normally oxygenated rabbits produces blood levels of FC12 which are stable and proportional to the rate of FC12 in the mixture. From the arterial concentration of 80 microgram/ml FC12 (10 % FC12) mixture) and over, FC12 alone causes effects proportional to doses: arterial pressure decrease with tachycardia; slight morphological alterations of the electrocardiogram at high concentration. Arrhythmia never occurs under the action of FC12 alone even at maximum arterial concentration reached here: 235 microgram/ml (40 % FC12 mixture). Recorded disturbances are always reversible. The intravenous perfusion of epinephrine alone evokes the appearance of premature contractions at only very high doses: 12 microgram/kg/min. The presence of FC12 in blood conjoined with epinephrine induces the inhibition of the hypertensive action of epinephrine at high concentrations and lowers the arrhythmogenic threshold. Both parameters interfere: the arrhythmogenic dose of epinephrine is a function of blood levels of FC12.     

Endogenous ghrelin and 5-HT regulate interdigestive gastrointestinal contractions in conscious rats

Endogenous ghrelin causes interdigestive contractions of the stomach in rats. In contrast, previous studies showed that 5-HT(3) and 5-HT(4) receptors were involved in regulating intestinal interdigestive contractions. We studied the possible role of endogenous ghrelin and 5-HT regulating interdigestive gastrointestinal (GI) contractions in rats. Four strain gauge transducers were implanted on the antrum, duodenum, and proximal and distal jejunum. After an overnight fast, GI contractions were recorded in freely moving conscious rats and ghrelin receptor antagonists [(d-lys3)GHRP6; 1 micromol/kg], 5-HT(3) antagonists (Ondansetron; 0.5 mg/kg) and 5-HT(4) antagonists (GR 125,487; 1 mg/kg) were administered (bolus iv). To evaluate the relationship between the luminal concentrations of 5-HT and phase III-like contractions of the duodenum, duodenal juice was collected via the intraduodenal catheter. 5-HT content of the duodenal juice was measured by HPLC. (d-lys3)GHRP6 significantly attenuated the occurrence and amplitude of phase III-like contractions of the antrum, but not the duodenum and jejunum. 5-HT(4) antagonists significantly reduced spontaneous phase III-like contractions of the jejunum, without affecting those of the antrum and duodenum. In contrast, 5-HT(3) antagonists did not affect phase III-like contractions in GI tract. Luminal concentration of 5-HT at the phase III-like contraction (36.0 +/- 13.3 ng/ml, n = 9) was significantly higher than that at the phase I-like contractions of the duodenum (4.9 +/- 1.6 ng/ml, n = 9, P < 0.05). It is suggested that released ghrelin from the gastric mucosa mediates gastric phase III-like contractions, whereas 5-HT released from enterochromaffin cells of the duodenal mucosa mediates intestinal phase III-like contractions via 5-HT(4) receptors.