Vagal Afferent Activity Research Articles

Jejunal or portal vein infusions of lipids increase hepatic vagal afferent activity.

Jejunal infusions of linoleic acid, corn oil, or caprylic acid significantly increased hepatic vagal afferent activity, whereas saline infusions were ineffective. The magnitude of response was greatest with either linoleic acid or corn oil. Hepatic portal infusions of linoleic acid, Liposyn II, or caprylic acid significantly increased hepatic vagal afferent activity, whereas 5% albumin/phosphate buffer vehicle was ineffective. The magnitude of response was greatest with either linoleic acid or Liposyn II. These data show that either jejunal or portal infusions of lipids increase activity of hepatic vagal afferents and could potentially serve as a complementary and/or alternative substrate to celiac vagal afferents in mediating the effects of jejunal infusions of lipids in suppressing food intake.

Hepato-vagal pathway associated with nicotine's anorectic effect in the rat

Nicotine reduces appetite and body weight. Because the hepato-portal area senses different types of nutrients that transmit signals via vagal afferent nerves to the hypothalamus to modify food intake and feeding pattern, we investigated the effect of nicotine on a hepato-vagal–hypothalamic pathway. Low doses of nicotine (<10 ng) injected into portal vein (ipv) decreased, while high doses of nicotine increased (≥10 ng) electrophysiological activity of hepatic vagal afferents. Stimulatory effect of high dose of nicotine on vagal hepatic afferents was blocked by a prior ipv injection of curare (30 μg) or hexamethonium (1 mg). Furthermore, activities of gastric vagal and adrenal sympathetic efferents were suppressed by low-dose, but stimulated by high-dose ipv nicotine. These reflex effects did not occur in hepatic vagotomized rats. Results of experiments demonstrate that in addition to nicotine's anorectic effect being mediated via a direct central action, nicotine also acts peripherally via hepatic vagal afferents from sensors of nicotine in the hepato-portal region.

The gut and food intake: an update for surgeons

Food intake is the simplest and most obvious measure of gastrointestinal function, yet it rarely receives more than cursory attention from surgeons. In this review we cover recent findings on relationships between gut function and appetite regulation mediated via neuropeptides influenced by afferent and efferent vagal activity. Evidence from the new discipline known as neurogastroenterology elucidates gastric and intestinal signals involved in the elicitation of hunger, satiety, and aversion. Discovery of the adipose-tissue—derived hormone, leptin, has energized the field of metabolism spawning increasing numbers of publications related to interactions between leptin and insulin release and glucose disposal, as well as appetitive behavior. Peptides such as cholecystokinin (CCK), the proglucagon-derived peptides, glucagon-like peptides 1 and 2 (GLP-1 and GLP-2), and the recently identified powerful intake-stimulating molecule, orexin, are examples of potential targets for drug development and studies of surgical pathophysiology. A major conclusion of this work is that the considerable redundancy and overlap between mediators of caloric intake subserving survival of the species, while beneficial after foregut surgery, contribute to the complexity of treating the global epidemic of obesity. Possibly knowledge derived from basic research in neurogastroenterology can translate into advances in surgical treatment of obesity.

Effects of CP-99, 994, a tachykinin NK 1 receptor antagonist, on abdominal afferent vagal activity in ferrets: evidence for involvement of NK 1 and 5-HT 3 receptors

The effect of CP-99, 994, a tachykinin NK 1 receptor antagonist, on abdominal vagal afferent nerve activity in the ferret was investigated. Substance P (1 μg/kg, i.v.) increased vagal afferent activity by 449.0±51.9% and this was reduced to 145.9±5.7% ( p<0.01) by pre-treatment with CP-99, 994 (1 mg/kg, i.v.), and to 149.5±1.5% ( p<0.001) by granisetron (1 mg/kg, i.v.), a 5-HT 3 receptor antagonist. In addition, the increase in vagal nerve activity induced by 5-HT (25 μg/kg, i.v., 552.0±57.0% increase from pre-injection level) was significantly reduced (401.3±10.6% increase from pre-injection level, p<0.05) by CP-99, 994 (100 μg/kg, i.v.). These results provide evidence for an involvement of peripheral NK 1 and 5-HT 3 receptors in substance P-induced vagal afferent activation. While the functional consequences (if any) of such peripheral effects were not investigated, they could contribute either directly (e.g. by blockade of receptors on vagal afferents) or indirectly (e.g. modulation of 5-HT release or reduction of local inflammatory response) to the antiemetic effects of CP-99, 994 against cisplatin and other emetic agents acting primarily via the vagus.

Activation of cardiac afferents by arachidonic acid: relative contributions of metabolic pathways.

Arachidonic acid (AA) is metabolized via cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P-450 (CP450) pathways to a variety of bioactive products. The sensitivity of cardiac afferent endings to AA and its metabolites, especially those derived from LOX and CP450 pathways, is currently unclear. We examined AA-induced activation of cardiac vagal chemosensitive afferents in non- and postischemic hearts in rats and evaluated the relative contributions of the three metabolic pathways to the effects. Epicardial application of AA activated the cardiac afferents dose dependently in both nonischemic and postischemic hearts, with afferent responses greater in the latter condition. In nonischemic hearts, the afferent response to AA was abolished only after simultaneous administration of indomethacin and 17-octadecynoic acid (COX and CP450 inhibitors, respectively). Nordihydroguaiaretic acid (a LOX inhibitor) had no effect on the afferent response to AA. In postischemic hearts, abolition of the afferent response to AA required simultaneous blockade of all three pathways. None of the AA metabolic inhibitors affected resting activity of cardiac afferents in nonischemic hearts, but each suppressed afferent activity during ischemia-reperfusion. Most COX metabolites, CP450 metabolites, and 5-LOX metabolites tested were capable of activating cardiac afferents. The 12-LOX metabolites and 15-LOX metabolites had no effect on afferent activity. These data indicate that in the nonischemic heart, basal AA metabolism does not contribute to resting afferent activity, but AA is capable of activating cardiac afferents via COX and CP450 but not LOX pathways. During ischemia-reperfusion, all three metabolic pathways contribute to activation of cardiac vagal afferents with an enhanced responsiveness to AA. Our results suggest that induction of the 5-LOX pathway contributes to the enhanced sensitivity of cardiac vagal afferents to AA in the ischemic condition.

Cardiac sympathetic afferent activation provoked by myocardial ischemia and reperfusion. Mechanisms and reflexes.

Cardiac sympathetic afferents are known to reflexly activate the cardiovascular system, leading to increases in blood pressure, heart rate, and myocardial contractile function. During myocardial ischemia, these sensory nerves also transmit the sensation of pain (angina pectoris) and cause tachyarrhythmias. The authors' laboratory has been interested in defining the mechanisms of activation of this neural system during ischemia and reperfusion. During these periods, reactive oxygen species, particularly hydroxyl radicals, are produced from the breakdown of purine metabolites and lead to stimulation of sympathetic (and vagal) ventricular chemosensitive nerve endings. For example, stimulation with hydrogen peroxide leads to a small reflex increase in blood pressure from the predominant sympathetic afferent activation that is reduced by simultaneous activation of cardiac vagal afferents (known to exert predominantly depressor reflexes). Central integration of these two opposing reflexes likely occurs at several regions of the brain stem, including the nucleus tractus solitarii, where neural occlusion occurs during simultaneous cardiac sympathetic and vagal-afferent stimulation. Activation of platelets also appears to play a role during myocardial ischemia, leading to local release of serotonin (5HT), which, through a 5HT3 mechanism, stimulates sympathetic afferents. Finally, regional changes in pH from lactic acid (but not hypercapnia), stimulate ventricular afferents and may activate kallikrein to increase bradykinin (BK), which, in turn, breaks down arachidonic acid to form prostaglandins. Prostaglandins sensitize cardiac sympathetic afferents to BK. Thus, stimulation of cardiac sympathetic afferents during ischemia and reperfusion and the resulting reflex events form a multifactorial process resulting from activation of a number of chemical pathways in the myocardium.

Spino-bulbo-spinal pathway mediating vagal modulation of nociceptive-neuroendocrine control of inflammation in the rat.

Stimulation of nociceptors by intradermal capsaicin produces depression of bradykinin (BK)-induced synovial plasma extravasation (PE) that is markedly enhanced by subdiaphragmatic vagotomy. This depression is mediated by the adrenal medullae, a propriospinal pathway between the afferent nociceptive input and preganglionic neurones projecting to the adrenal medullae, and a spino-bulbo-spinal pathway. Here we investigated the role of spinal ascending and descending pathways in the interaction between noxious and vagal afferent inputs, leading to inhibition of BK-induced PE mediated by the adrenal medullae. Nociceptors in the paw were activated by capsaicin and depression of BK-induced PE was measured in rats with intact or cut subdiaphragmatic vagus nerves. After cutting the dorsolateral funiculus (DLF) contralateral to the stimulated hindpaw (segmental level C5/C6 and T8/T9), depression of BK-induced PE was weak or absent both in rats with intact vagus nerves and in vagotomised rats, suggesting that an ascending excitatory pathway was interrupted. After cutting the DLF ipsilateral to the stimulated hindpaw, depression of BK-induced PE was already markedly enhanced, even in the absence of vagotomy. Ipsilateral DLF lesion (L2/L3) below the level of the spinal output to the adrenal medullae produced the same effect, suggesting interruption of a descending inhibitory pathway that relays the effect of vagal activity to the level of the capsaicin-induced nociceptive input. Contralateral and ipsilateral hemisection of the spinal cord (C5/C6) produced the same changes as the corresponding DLF lesions. Ipsi- or contralateral lesion of the dorsal funiculus at the spinal level T8/T9 had no effect on depression of BK-induced PE generated by cutaneous noxious stimulation of the forepaw. We suggest that noxious stimulation activates an ascending pathway of the spino-bulbo-spinal excitatory circuit which projects through the DLF contralateral to the nociceptive input, and that the inhibitory pathway which is activated by vagal afferent activity projects through the DLF ipsilateral to the nociceptive input.

Lung vagal afferent activity in rats with bleomycin-induced lung fibrosis

Bleomycin treatment in rats results in pulmonary fibrosis that is characterized by a rapid shallow breathing pattern, a decrease in quasi-static lung compliance and a blunting of the Hering–Breuer Inflation Reflex. We examined the impulse activity of pulmonary vagal afferents in anesthetized, mechanically ventilated rats with bleomycin-induced lung fibrosis during the ventilator cycle and static lung inflations/deflations and following the injection of capsaicin into the right atrium. Bleomycin enhanced volume sensitivity of slowly adapting stretch receptors (SARs), while it blunted the sensitivity of these receptors to increasing transpulmonary pressure. Bleomycin treatment increased the inspiratory activity, while it decreased the expiratory activity of rapidly adapting stretch receptors (RARs). Pulmonary C-fiber impulse activity did not appear to be affected by bleomycin treatment. We conclude that the fibrosis-related shift in discharge profile and enhanced volume sensitivity of SARs combined with the increased inspiratory activity of RARs contributes to the observed rapid shallow breathing of bleomycin-induced lung fibrosis.

Vagal afferent activity and body temperature in 3 to 10-day-old and adult rats

This study examined the possible contribution of vagal stretch receptor activity to the increased power of the Hering-Breuer reflex in hyperthermia in rats during the early postnatal period. Experiments were performed on 10 anesthetized (pentobarbital 40 mg/kg, i.p.) 3 to 10-day-old (body weight of 16 +/- 1 g; SE) and, for comparison, 18 adult Sprague-Dawley rats (body weight of 336 +/- 35 g). Animals were tracheostomized and artificially ventilated with oxygen. The left vagus nerve was cut. In adult animals, single receptor fibers or a bundle of a few fibers were recorded using a bipolar stainless-steel electrode under mineral oil. In the young rats, a suction electrode filled with normal saline was used. Positive pressure of either 5 or 10 cmH2O was applied to the trachea when the respirator was turned off. The vagal activity was amplified and monitored on a storage oscilloscope for calculation of the frequency of vagal afferent activity during a given pressure application at different rectal temperatures (T(R); range 28 to 42 degrees C). In total, 30 and 31 sets of vagal activity in the young and adult rats, respectively, were analyzed. In all cases, an increase in tracheal pressure (P(TR)) from 5 to 10 cmH2O increased the frequency of vagal firing. The increase was greater in the adult versus the young animals; at 36 degrees C the increase was 49 +/- 11% and 16 +/- 3% in the adult and young rats, respectively (P < 0.01). In all animals, vagal receptors showed temperature-sensitivity, but less so in the young than in the adult rats (P < 0.0004 and P < 0.003; for P(TR) of 5 and 10 cmH2O, respectively). In addition, the relationship between temperature-sensitivity and T(R) had significant slopes (P < 0.001 for both inflation pressures) in the adults but not in the young rats, indicating that in the latter the temperature-sensitivity of vagal receptors is independent of TR. These results imply that temperature-sensitivity of vagal receptors could have contributed to the increased power of the Hering-Breuer reflex in rats during the early postnatal period in the warmer environment.

The contribution of the vagus nerve in interleukin-1beta-induced fever is dependent on dose.

It has been suggested that proinflammatory cytokines communicate to the brain via a neural pathway involving activation of vagal afferents by interleukin-1beta (IL-1beta), in addition to blood-borne routes. In support, subdiaphragmatic vagotomy blocks IL-1beta-induced, brain-mediated responses such as fever. However, vagotomy has also been reported to be ineffective. Neural signaling would be expected to be especially important at low doses of cytokine, when local actions could occur, but only very small quantities of cytokine would become systemic. Here, we examined core body temperature after intraperitoneal injections of three doses of recombinat human IL-1beta (rh-IL-1beta). Subdiaphragmatic vagotomy completely blocked the fever produced by 0.1 microg/kg, only partially blocked the fever produced by 0.5 microg/kg, and had no effect at all on the fever that followed 1.0 microg/kg rh-IL-1beta. Blood levels of rh-IL-1beta did not become greater than normal basal levels of endogenous rat IL-beta until the 0.5-microg/kg dose nor was IL-1beta induced in the pituitary until this dose. These results suggest that low doses of intraperitoneal IL-1beta induce fever via a vagal route and that dose may account for some of the discrepancies in the literature.

Gender and gonadal hormone effects on vagal modulation of tonic nociception

We studied the influence of gender and gonadal hormones on modulation of tonic nociception exerted by vagal activity. In male rats, subdiaphragmatic vagotomy resulted in significantly reduced nociceptive behavior during phase 2 of the formalin test. Whereas gonadectomy alone had no effect, it completely eliminated the suppressive effect of subdiaphragmatic vagotomy; however, sex hormone replacement with either testosterone or dihydrotestosterone did not restore the ability of subdiaphragmatic vagotomy to suppress nociceptive behavior. These results suggest that, in males, a gonad-dependent but androgenic gonadal hormone-independent mechanism contributes to pronociceptive effects of vagal afferent activity. Although neither gonadectomy nor subdiaphragmatic vagotomy alone affected the response to formalin in females, gonadectomy plus vagotomy resulted in significantly reduced nociceptive behavior during phase 2. Reconstitution with 17β-estradiol implants in gonadectomized females not only prevented suppression of nociceptive behavior seen with gonadectomy plus vagotomy, but also led to increased nociceptive behavior in the interphase between phases 1 and 2. However, placement of 17β-estradiol implants in gonad-intact females had no effect on formalin-induced nociceptive behavior. The finding that estrogen produced an increase in nociceptive behavior in gonadectomized female rats after vagotomy but not in normal female rats (with intact gonads and subdiaphragmatic vagus) suggests that the interaction between estrogen and nociceptive afferent activity is suppressed by vagal function. In conclusion, a nonandrogenic action of testicular function in male rats and estrogen in females seems to influence the effect of vagal activity on formalin-induced nociceptive behavior.

Vagal afferent activity and body temperature in 3 to 10-day-old and adult rats

Vagal afferent activity and body temperature in 3 to 10-day-old and adult rats

Effect of interleukin-1β on subdiaphragmatic vagal efferents in the rat

Interleukin-1β (IL-1β) is an important mediator of fever and illness. Recent studies have demonstrated that IL-1β (2 μg kg −1) increases gastric vagal afferent activity. The peripheral mechanisms of the action of lower doses were studied by recording the mass efferent and afferent activity of the gastric branch of the ventral vagal nerve in anesthetized rats. Twenty min after i.v. administration of IL-1β (1 μg kg −1) the efferent activity of the vagal nerve was decreased to 62±6% in totally but not in partly vagotomized rats. Preadministration of indomethacin (5 mg kg −1) 30 min before IL-1β blocked this reduction. Administration of 1 μg kg −1 of IL-1β had no effect on the afferent activity of the gastric branch of the vagal nerve. The present results suggest that the subdiaphragmatic vagal afferents modulate the parasympathetic efferent outflow in response to IL-1β partly through prostaglandin dependent mechanisms and that supradiaphragmatic afferents or central sites are more sensitive to the low doses of IL-1β which becomes evident after elimination of the subdiaphragmatic vagal input.

Neurochemistry and neuropharmacology of emesis — the role of serotonin

Emesis is an instinctive defense reaction caused by the somato-autonomic nerve reflex which is integrated in the medulla oblongata. Emesis caused by cytotoxic drugs and radiation is associated with an increase in the concentration of 5-hydroxytryptamine (5-HT) in the intestinal mucosa and in the brainstem. 5-HT released from enterochromaffin (EC) cells, which synthesize and secrete 5-HT, stimulates the 5-HT 3 receptors on the adjacent vagal afferent nerves. This vagal afferent nerve depolarization may evoke the vomiting reflex. This review describes the role of 5-HT in anticancer drug-induced emesis from the viewpoint of 5-HT release from EC cells and afferent vagus nerve activity.

Slow hyperpolarization in cortical neurons: a possible mechanism behind vagus nerve simulation therapy for refractory epilepsy?

Recent studies have shown that chronic, intermittent stimulation of the left vagus nerve (VNS) decreases the frequency, duration, and/or intensity of seizures in some patients with medically refractory focal seizures. Although VNS is being used in an increasing number of patients, the neuronal mechanism behind VNS therapy of refractory epileptic seizures is yet unclear. In vivo intracellular recordings were used to study responses elicited by the VNS in pyramidal neurons of the parietal association cortex in anesthetized rats. Low-intensity trains of VNS, which activated predominantly myelinated fibers (100 microA, 30 Hz, 0.5 millisecond, 20 seconds), elicited a slow hyperpolarization (onset latency 17.4 +/- 2.0 seconds, amplitude -4. 7 +/- 0.6 mV, duration 35 +/- 3.2 seconds; n = 19). Increasing the intensity of VNS to recruit nonmyelinated vagal fibers (200 microA) led to an increase in the magnitude of the response in some neurons while failed to evoke a response in others. On increasing the stimulus intensity to 500 microA, only one in nine neurons exhibited a visible response. All recorded and visualised neurons were pyramidal cells in cortical layer V. Stimulus intensities that activate predominantly myelinated fibers (less than 200 microA) were most effective to induce slow vagal hyperpolarization. It is suggested that slow hyperpolarization may be one of the mechanisms that underlie the seizure-reducing effect of VNS, by means of reducing the excitability in neurons that would be involved in propagation of seizure activity. As the balance of activity in myelinated and nonmyelinated primary vagal afferents influenced the effect of VNS stimulation, it is likely that the effect of VNS is modulated as changes occur in the underlying vagal tone.

Oxidative stress impairs cardiac chemoreflexes in diabetic rats.

We investigated the effects of diabetes mellitus and antioxidant treatment on the sensory and reflex function of cardiac chemosensory nerves in rats. Diabetes was induced by streptozotocin (STZ; 85 mg/kg ip). Subgroups of sham- and STZ-treated rats were chronically treated with an antioxidant, vitamin E (60 mg/kg per os daily, started 2 days before STZ). Animals were studied 6-8 wk after STZ injection. We measured renal sympathetic nerve activity (RSNA), mean arterial blood pressure (MABP), and cardiac vagal and sympathetic afferent activities in response to stimulation of chemosensitive sensory nerves in the heart by epicardial application of capsaicin (Caps) and bradykinin (BK). In cardiac sympathetic-denervated rats, Caps and BK (1-10.0 microg) evoked a vagal afferent mediated reflex depression of RSNA and MABP, which was significantly blunted in STZ-treated rats (P < 0.05). In vagal-denervated rats, Caps and BK (1-10.0 microg) evoked a sympathetic afferent-mediated reflex elevation of RSNA and MABP, which also was significantly blunted in STZ-treated rats (P < 0.05). Chronic vitamin E treatment effectively prevented these cardiac chemoreflex defects in STZ-treated rats without altering resting blood glucose or hemodynamics. STZ-treated rats with insulin replacement did not exhibit impaired cardiac chemoreflexes. In afferent studies, Caps and BK (0.1 g-10.0 microg) increased cardiac vagal and sympathetic afferent nerve activity in a dose-dependent manner in sham-treated rats. These responses were significantly blunted in STZ-treated rats. Vitamin E prevented the impairment of afferent discharge to chemical stimulation in STZ rats. The following were concluded: STZ-induced, insulin-dependent diabetes in rats extensively impairs the sensory and reflex properties of cardiac chemosensitive nerve endings, and these disturbances can be prevented by chronic treatment with vitamin E. These results suggest that oxidative stress plays an important role in the neuropathy of this autonomic reflex in diabetes.

Effects of systemic injection of interleukin-1β on gastric vagal afferent activity in rats lacking type A cholecystokinin receptors

We have shown that systemic administration of interleukin-1β (IL-1β) excites gastric vagal afferent activity in part via stimulation of type A cholecystokinin (CCK-A) receptors in rats. The present study was undertaken to determine whether the response of the gastric vagal afferent nerve to systemic IL-1β is altered in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, which lack CCK-A receptors. The response was compared with that of the control strain, Long-Evans Tokushima Otsuka (LETO) rats. All animals were anesthetized with pentobarbital and artificially ventilated. Intravenous administration of 4 μg/kg of IL-1β increased gastric vagal afferent activity in both LETO and OLETF rats, whereas a smaller dose of 2 μg/kg of IL-1β increased activity only in the OLETF rats. The present results demonstrate that the response of the gastric vagal afferent activity in CCK-A receptor deficient OLETF rats was more sensitive to intravenous administration of IL-1β than was in control LETO rats.

Oral serotonin type 3-receptor antagonists for prevention of chemotherapy-induced emesis.

The theoretical basis for and clinical experience with using oral serotonin type 3 (5-HT3)-receptor antagonists for preventing chemotherapy-induced emesis are discussed. Evidence supports the idea that antineoplastic drugs and irradiation can initiate emesis by releasing serotonin from enterochromaffin cells in the gut mucosa, which activates peripheral vagal afferent nerves. In view of the GI site of serotonin release and vagal afferent activation, the proximity of neuronal 5-HT3 receptors, and the pharmacologic properties of 5-HT3-receptor antagonists, the oral use of these agents is rational. Oral granisetron 2 mg once daily or 1 mg twice daily has been evaluated in more than 4500 patients receiving highly or moderately emetogenic chemotherapy. Rates of total control of emesis ranged from 44% to 60%, and complete-response rates ranged from 70% to 94%. Oral ondansetron 8 mg three times daily has proven effective in patients receiving antineoplastics with moderate or moderately high emetogenic potential. Two double-blind studies demonstrated the efficacy of a single 24-mg oral dose of ondansetron administered approximately 30 minutes before cisplatin-based chemotherapy. Patients randomized to oral ondansetron had higher total-control and complete-response rates than patients receiving intravenous granisetron or ondansetron. Oral dolasetron 100 or 200 mg once daily also prevented emesis. Oral administration of 5-HT3-receptor antagonists for the prevention of acute emesis associated with chemotherapy is rational and appears to be effective.

Intrapericardiac injections of algogenic chemicals excite primate C1-C2 spinothalamic tract neurons.

Extracellular potentials of 38 C1-C2 spinothalamic tract (STT) neurons in anesthetized monkeys (Macaca fascicularis) were examined for responses to intrapericardiac injections of an algogenic chemical mixture (adenosine, 10(-3) M; bradykinin, prostaglandin E(2), serotonin, histamine, each 10(-5) M). Chemical stimulation of cardiac/pericardiac receptors increased activity of 21 cells, decreased activity of 5 cells, and did not change activity of 12 cells. Cells excited by chemical stimuli received input from noxious mechanical stimulation of somatic fields; most receptive fields included the neck, inferior jaw, or head areas. Nerve ablations in 11 cells excited by intrapericardiac chemicals showed that cardiac input activated by algogenic chemicals traveled primarily in vagal afferent fibers to C1-C2 segments; phrenic or cardiopulmonary sympathetic inputs were predominant in 2 of 11 cells. These results supported the concept that activation of cardiac vagal afferents might lead to the production of referred pain sensation in somatic fields innervated from high cervical segments.

Exogenous cholecystokinin-8 reduces vagal efferent nerve activity in rats through CCK(A) receptors.

It has been proposed that the vagus nerve plays a role in mediating cholecystokinin-8 (CCK-8) effect on such gastric functions as motility, emptying and gastric acid secretion. To examine the contribution of the efferent pathways in realizing these effects, efferent mass activity in the ventral gastric vagal nerve in Sprague-Dawley rats was recorded. Intravenous infusion of CCK-8 (0.1-1 nmol) suppressed the efferent activity. The effect of CCK-8 was significantly reduced in animals with total subdiaphragmatic vagotomy in comparison to those with partial vagotomy. Intravenous infusion of CCK(A) receptor antagonist L-364,718 (1-100x10(-6) g) blocked the response of vagal efferent activity to 0.1 nmol CCK-8, but the CCK(B) receptor antagonist L-365,260 (1-100x10(-6) g) did not in the conditions of either partial or total vagotomy. Intracisternal infusion of L-364,718 (1x10(-6) g) blocked the response of vagal efferent activity to 0.1 nmol CCK-8 i.v. Infusion of exogenous CCK-8 did not affect the activity of supradiaphragmatic vagal afferents. The results suggest that the effect of systemically administered CCK-8 on vagal efferent activity is mediated by both peripherally (subdiaphragmatically) and centrally localized CCK(A) receptors.