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In rabbit carotid bodies (CBs) superfused during 1-5 h, with an air-equilibrated medium containing no tyrosine (TYR), the dopamine (DA) content decreased by approximately 60% after 1 h and remained constant afterwards. TYR and 3,4-dihydroxyphenylacetic acid (DOPAC) decreased with the same time course. Noradrenaline (NA) content exhibited a biphasic decrease of lesser magnitude than that of DA. Superfusions with a TYR-containing medium did not prevent the reduction in DA and TYR. Large amounts of DA and DOPAC were recovered in the effluent during the first hour of superfusion but after 90 min the two substances had declined below the detection limits (i.e. 0.5 and 1 pmol/5 min, respectively). The DA efflux decreased exponentially during the first hour and was not altered by changing the oxygen partial pressure (PO2) of the medium. The DOPAC efflux declined after 40 min of superfusion and was modulated by PO2. The DA and the DOPAC effluxes were not suppressed by omitting calcium ions from the superfusing medium. In 4 cat CBs equal amounts of DA and NA were recovered from the effluent during the first hour of superfusion.

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The monoamine and catabolite contents of a large number of rabbit (n = 95) and cat (n = 32) carotid bodies (CBs) have been measured by high performance liquid chromatography with electrochemical detection (HPLC-ED). The dopamine (DA) content as well as that of its precursors tyrosine (TYR), dihydroxyphenylalanine (DOPA) and catabolites dihydroxyphenylacetic acid (DOPAC), homovanilic acid (HVA) were approximately equal in both species. The noradrenaline (NA) content was 10 times larger in the cat than in the rabbit CBs. Twenty-nine out of the 32 cat CBs contained more NA than DA while the reverse was true in 92 out of 95 rabbit CBs. In 11 cats the right CB was sympathectomized and its DA and NA contents were compared to those of intact contralateral organs.

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In the rabbit carotid body (CB) in vivo, the rate of dopamine metabolism was estimated to 44.4 +/- 3.9 (SD) pmol/CB/h from the decrease in dihydroxyphenylacetic acid content after pargyline inhibition of monoamine oxidase.

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Monoamines and their metabolites have been measured by high performance liquid chromatography with electrochemical detection, in control rabbit carotid bodies and under several experimental conditions: 1) at different times (3 h, 6 h, 24 h, 48 h) after intravenous injection of reserpine (5 mg/kg); 2) 14 days after sympathectomy; 3) 14 days after section of the carotid sinus nerve. The results were analyzed with probability plotting methods. Dopamine was the most important monoamine in the carotid body (CB) and its variations were very large. It was almost entirely depleted by reserpinization without simultaneous increase in 3,4-dihydroxyphenylacetic acid. Sympathectomy increased dopamine content but did not change noradrenaline content. However data analysis suggested that noradrenaline might be compartmented in two pools: one with a large variance, located in the type I cells was increased after sympathectomy, the other, more constant, located in the sympathetic nerve endings was entirely depleted after sympathectomy. Section of the carotid sinus nerve increased dopamine and noradrenaline and quadrupled the serotonin content of the CB. It is proposed that carotid sinus and sympathetic innervations regulate the monoamine metabolism of the CB.

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Dialysis fibers chronically implanted into the gastric submucosa of rabbits allowed us to collect an interstitial fluid (I.S.F.) dialysate in which biogenic amine concentrations were measured, and compared with those obtained from plasma and tissue samples. The results suggest that I.S.F. concentrations represent a good assessment of the local release of the amines by enteric nerves and/or paracrine cells, under basal conditions. The fact that acetylcholine and neostigmine, when perfused through the dialysis system, increased I.S.F. serotonin (5-HT) concentrations, supports a cholinergic modulation of the release of 5-HT within the gastrointestinal wall, and validates the dialysis method as a powerful tool to monitor, in vivo, dynamic changes in I.S.F. monoamine concentrations.

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Monoamine metabolites in the lumbar cerebrospinal fluid were measured by high-performance liquid chromatography with electrochemical detection (HPLC-ECD) in 6 conscious dogs after administration of morphine. The concentrations of dopamine and its metabolites exhibited only small variations whereas a significant increase in serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) occurred after a latency of 5 min and culminated after 1 h. The increased release of 5-HT and 5-HIAA and behavioral changes (restlessness, sialorrhea) induced by morphine were prevented by administration of naloxone or nalorphine.

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Assays capable of concurrently measuring small quantities of noradrenaline, dopamine, serotonin, and several of their metabolites in cerebrospinal fluid (c.s.f.) were developed by the use of high performance liquid chromatography with electrochemical detection. For comparison, cortical subarachnoid, ventricular, cisternal and lumbar c.s.f. were obtained by puncture under barbiturate anaesthesia in sheep. Basal concentrations related to the adrenergic system, including methoxyhydroxyphenylglycol (MHPG), were similar in ventricular, cisternal and lumbar c.s.f., and those of the serotoninergic metabolites, 5-hydroxyindole-3-acetylacetic acid (5-HIAA), were similar in ventricular and cisternal c.s.f. High concentrations of the dopamine metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), were found only in ventricular c.s.f. Monoamine metabolites in ventricular c.s.f. under basal conditions and after various experimental manipulations were then determined over periods of 3 months in two different breeds of sheep fitted chronically with cannulae in lateral ventricles. A dose-related accumulation of all the acidic monoamine metabolites was recorded during treatment with probenecid. The increase in 5-HIAA was linear after administration of increased doses of tryptophan and 5-hydroxytryptophan. The concentrations of dopamine, DOPAC and HVA in the ventricular c.s.f. reflected the response of the dopaminergic system to agents capable of crossing the blood-brain barrier. It is concluded that cerebral metabolism in conscious sheep could be indirectly approached by recording the concentration of end-products of dopamine metabolism in ventricular cerebrospinal fluid, obtained under conditions of minimal stress.

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Myoelectrical and mechanical activities were chronically recorded by use of nichrome electrodes and miniaturized strain-gage transducers sutured on the serosa of the antrum, the duodenum, and the jejunum. In a first experiment (n = 6 rats) the early (0-6 h) and late (greater than 4 days) effects of streptozotocin (65 mg/kg i.v.) was recorded. In addition, the effect of insulin (1-5 IU/kg) and glucagon (6-200 micrograms/kg) administered intravenously were studied separately each in groups of seven normal and streptozotocin-induced diabetic-fed and fasted rats. The results indicated that within the 30 min following streptozotocin administration there was a significant stimulation of the duodenal and jejunal motility lasting 46 +/- 8 min. When diabetes was established as shown by the basal blood glucose level obtained in those rats (2.30 +/- 0.84 g/L), a progressive decrease of the frequency of the migrating myoelectric complex was observed along with a disorganization of the regular spiking activity phases without disturbing the basal electrical rhythm. Comparing with the basal level, a significant increase in the gastrointestinal motility indexes (MI) appeared both in fasted (p less than 0.01) and fed (p less than 0.05) normal animals, 13.1 +/- 1.6 min after an i.v. injection of 1 IU/kg insulin. Motor effects of glucagon were related to the dose. When used at 25 microgram/kg a disorganization of the spiking activity was observed with a stimulation of the contractile activity in the jejunum. At higher dosages, i.e., 100 micrograms/kg, it induced an immediate and significant decrease of motility at any level tested and lasting up to 20 +/- 7 min. The motility responses to both hormones were lower in diabetic than in normal rats.

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Blood concentration of reducing sugar and electrical activity of the duodenum were simultaneously measured in four conscious pigs, each chronically fitted with a catheter in a jugular vein, a duodenal infusion catheter, and transparietal intestinal electrodes. After a meal, blood sugar concentration exhibited cyclic variations at a frequency similar to that of the migrating myoelectric complexes (MMC) observed on the duodenum (1.6 +/- 0.3 per h). During the fasting state (15 h), glucose or xylose infusions into the duodenum also induced blood sugar oscillations at the same frequency as that of duodenal MMC (0.9 +/- 0.3 per h). Injections of xylose boluses into the duodenum induced more rapid and larger increases in blood reducing sugar concentration when injected during the last two-thirds of the phase of irregular spiking activity or during the phase of regular spiking activity than when injected during quiescence or the first third of the phase of irregular spiking activity. It is concluded that intestinal motility is a prerequisite for optimal intestinal absorption of sugar that is markedly enhanced at the time of maximal digesta flow in the pig.

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The effects of increased doses (0.05-02 mg/kg) of morphine and nalorphine on colonic motility were investigated in 15-22 h fasted dogs fitted with two strain gauge transducers on the transverse colon at 8 and 15 cm from the ileo-colonic junction. These effects were compared to those obtained after previous administration of naloxone (0.3 mg/kg), atropine (0.1 mg/kg) and methysergide (0.1 mg/kg). Both morphine and nalorphine, at a dose of 0.1 mg/kg increased the colonic motility index by 285 and 248% from 0 to 60 min respectively after their administration, these effects lasting 3.2 and 2.6 h. These stimulatory effects were abolished by previous administration of naloxone (0.3 mg/kg) or atropine (0.1 mg/kg) and limited to 60 min after methysergide (0.1 mg/kg). It was concluded that nalorphine may be considered as a potent morphinomimetic substance upon colonic motility and that cholinergic and serotonergic receptors were involved in the colonic response to morphine.

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The chronically-prepared gut is a very useful model for the determination of the motor profile changes due to drugs in both fed and unfed animals. Rats fitted with strain gauge transducers and implanted electrodes showed a good relationship between motility indices of spiking activity and mechanical activity. In both fed and fasted rats records of contractions of the antrum gave a more accurate representation, as tonic changes in antral activity can be seen. On the other hand, the electrical spiking activity of the small intestine allows more accurate recording of pharmacological responses than recording of the mechanogram. These variations as well as the changes in the duration of quiescence may be of importance in the quantitative assessment of the gastrointestinal motor profile.

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Relationships between the basic motor patterns of the small bowel, i.e. the occurrence at hourly intervals of myoelectric complexes and absorption of glucose were studied in vivo on 2-m length ovine jejunum isolated loops by means of the "perfusion marker" technique. For a mean flow rate of about 480 ml/h, the net glucose movement during queiscence was decrease at the occurrence of the phase of irregular spiking activity (ISA) and increased during the phase of regular spiking activity (RSA) of the myoelectric complex. When the flow rate was nearly halved (225 ml/h), the net absorption of glucose was decreased at the occurrence of the phases of either ISA or RSA of the complexes.

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The effect of insulin on jejunal myoelectric activity was studied in conscious dogs and sheep by injection of insulin and stimulation of insulin release. In dogs, the migrating myoelectric complex (MMC), characteristic of fasting, was replaced by a continuous pattern of activity after feeding, injection of insulin, or infusion of D-glucose, L-leucine, or L-arginine. The response to feeding was reduced in alloxan-diabetic dogs and completely abolished following additional vagotomy when only exogenous insulin induced the "fed" pattern. Vagotomy alone had only minor effects on the response to feeding. Sheep exhibit a continuous sequence of MMC, regardless of feeding, but infusion of insulin or volatile fatty acids produced activity similar to that seen after feeding in dogs. In alloxan-diabetic sheep the recurrence and intensity of the MMC were decreased, and the effect of volatile fatty acids was eliminated. Insulin injection restored the pattern to normal. Thus, insulin levels are of importance in the control of the jejunal motor profile and may mediate the postprandial disappearance of MMC in dogs.

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In dogs after feeding increased plasma insulin concentration is positively related in converting the "fasted" pattern of electrical activity into the "fed" pattern. In sheep, the release of insulin induced by a perfusion of volatile fatty acids is accompanied by similar changes in the pattern of electrical activity. The results indicate that insulin release induced by nutrients plays a major role in the control of intestinal motility in both species.

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