Biomedical subjects

T A Day

Publications and source records attributed to T A Day.

At least 55 records · Page 3Linked to original sources

PubMed1999

Parasitic peptides! The structure and function of neuropeptides in parasitic worms.

Parasitic worms come from two very different phyla-Platyhelminthes (flatworms) and Nematoda (roundworms). Although both phyla possess nervous systems with highly developed peptidergic components, there are key differences in the structure and action of native neuropeptides in the two groups. For example, the most abundant neuropeptide known in platyhelminths is the pancreatic polypeptide-like neuropeptide F, whereas the most prevalent neuropeptides in nematodes are FMRFamide-related peptides (FaRPs), which are also present in platyhelminths. With respect to neuropeptide diversity, platyhelminth species possess only one or two distinct FaRPs, whereas nematodes have upwards of 50 unique FaRPs. FaRP bioactivity in platyhelminths appears to be restricted to myoexcitation, whereas both excitatory and inhibitory effects have been reported in nematodes. Recently interest has focused on the peptidergic signaling systems of both phyla because elucidation of these systems will do much to clarify the basic biology of the worms and because the peptidergic systems hold the promise of yielding novel targets for a new generation of antiparasitic drugs.

Amino Acid Sequence↗

PubMed1999

The central amygdala modulates hypothalamic-pituitary-adrenal axis responses to systemic interleukin-1beta administration.

In the present study we examined the role of the central nucleus of the amygdala in hypothalamic-pituitary-adrenal axis responses to an immune challenge in the form of systemic administration of the proinflammatory cytokine interleukin-1beta (1 microg/kg). We found that bilateral ibotenic acid lesions of the central amygdala substantially reduced adrenocorticotropin hormone release and hypothalamic corticotropin-releasing factor and oxytocin cell c-fos expression responses to interleukin-1,8 suggesting a facilitatory role for this structure in the generation of hypothalamic-pituitary-adrenal axis responses to an immune challenge. Since only a small number of central amygdala cells project directly to the paraventricular nucleus, we then examined the effect of central amygdala lesions on the activity of other brain nuclei that might act as relay sites in the control of the hypothalamic-pituitary-adrenal axis function. We found that bilateral central amygdala lesions significantly reduced interleukin-1beta-induced c-fos expression in cells of the ventromedial and ventrolateral subdivisions of the bed nucleus of the stria terminalis and brainstem catecholamine cell groups of the nucleus tractus solitarius (A2 noradrenergic cells) and ventrolateral medulla (A1 noradrenergic and C1 adrenergic cells). These findings, in conjunction with previous evidence of bed nucleus of the stria terminalis and catecholamine cell group involvement in hypothalamic-pituitary-adrenal axis regulation, suggest that ventromedial and ventrolateral bed nucleus of the stria terminalis cells and medullary catecholamine cells might mediate the influence of the central amygdala on hypothalamic-pituitary-adrenal axis responses to an immune challenge. Thus these data establish that the central amygdala influences hypothalamic-pituitary-adrenal axis responses to a systemic immune challenge but indicate that it primarily acts by modulating the activity of other control mechanisms.

Adrenocorticotropic Hormone↗

PubMed1999

Neuroendocrine responses to an emotional stressor: evidence for involvement of the medial but not the central amygdala.

The amygdala plays a pivotal role in the generation of appropriate responses to emotional stimuli. In the case of emotional stressors, these responses include activation of the hypothalamic-pituitary-adrenal (HPA) axis. This effect is generally held to depend upon the central nucleus of the amygdala, but recent evidence suggests a role for the medial nucleus. In the present study, c-fos expression, amygdala lesion and retrograde tracing experiments were performed on adult rats in order to re-evaluate the role of the central as opposed to the medial amygdala in generating neuroendocrine responses to an emotional stressor. Brief restraint (15 min) was used as a representative emotional stressor and was found to elicit c-fos expression much more strongly in the medial than central nucleus of the amygdala; relatively few Fos-positive cells were seen in other amygdala nuclei. Subsequent experiments showed that ibotenic acid lesions of the medial amygdala, but not the central amygdala, greatly reduced restraint-induced activation of cells of the medial paraventricular nucleus, the site of the tuberoinfundibular corticotropin-releasing factor cells that constitute the apex of the HPA axis. Medial amygdala lesions also reduced the activation of supraoptic and paraventricular nucleus oxytocinergic neurosecretory cells that commonly accompanies stress-induced HPA axis activation in rodents. To assess whether the role of the medial amygdala in the control of neuroendocrine cell responses to emotional stress might involve a direct projection to such cells, retrograde tracing of amygdala projections to the paraventricular nucleus was performed in combination with Fos immunolabelling. This showed that although some medial amygdala cells activated by exposure to an emotional stressor project directly to the paraventricular nucleus, the number is very small. These findings provide the first direct evidence that it is the medial rather than the central amygdala that is critical to hypothalamic neuroendocrine cell responses during an emotional response, and also provide the first evidence that the amygdala governs oxytocin as well as HPA axis responses to an emotional stressor.

Amygdala↗

PubMed1999

Pharmacology of FMRFamide-related peptides in helminths.

Nervous systems of helminths are highly peptidergic. Species in the phylum Nematoda (roundworms) possess at least 50 FMRFamide-related peptides (FaRPs), with more yet to be identified. To date, few non-FaRP neuropeptides have been identified in these organisms, though evidence suggests that other families are present. FaRPergic systems have important functions in nematode neuromuscular control. In contrast, species in the phylum Platyhelminthes (flatworms) apparently utilize fewer FaRPs than do nematodes; those species examined possess one or two FaRPs. Other neuropeptides, such as neuropeptide F (NPF), play key roles in flatworm physiology. Although progress has been made in the characterization of FaRP pharmacology in helminths, much remains to be learned. Most studies on nematodes have been done with Ascaris suum because of its large size. However, thanks to the Caenorhabditis elegans genome project, we know most about the FaRP complement of this free-living animal. That essentially all C. elegans FaRPs are active on at least one A. suum neuromuscular system argues for conservation of ligand-receptor recognition features among the Nematoda. Structure-activity studies on nematode FaRPs have revealed that structure-activity relationship (SAR) "rules" differ considerably among the FaRPs. Second messenger studies, along with experiments on ionic dependence and anatomical requirements for activity, reveal that FaRPs act through many different mechanisms. Platyhelminth FaRPs are myoexcitatory, and no evidence exists of multiple FaRP receptors in flatworms. Interestingly, there are examples of cross-phylum activity, with some nematode FaRPs being active on flatworm muscle. The extent to which other invertebrate FaRPs show cross-phylum activity remains to be determined. How FaRPergic nerves contribute to the control of behavior in helminths, and are integrated with non-neuropeptidergic systems, also remains to be elucidated.

Amino Acid Sequence↗

PubMed1999

Resistance to praziquantel: direct evidence from Schistosoma mansoni isolated from Egyptian villagers.

Recent evidence suggest that resistance to praziquantel (PZQ) may be developing. This would not be surprising in countries like Egypt where the drug has been used aggressively for more that 10 years. The classic phenotype of drug resistance is a significant increase in the 50% effective dose value of isolates retrieved from patients not responding to the drug. In a previous publication, we reported that such phenotypes have been isolated from humans infected with Schistosoma mansoni. Since the action of PZQ may be dependent upon the drug and host factors, most notably the immune system, we analyzed the quantitative effects of PZQ on single worms that differed in their response to PZQ when maintained in mice. Our hypothesis was that the in vitro action of the drug would correlate with it in vivo action. We confirmed this hypothesis and conclude that the in vitro action of the drug is related to its in vivo action. Knowing this relationship will assist in our ability to detect or survey for the PZQ resistant phenotype in human populations.

Animals↗

PubMed1998

The metalloprotease inhibitor 1,10-phenanthroline affects Schistosoma mansoni motor activity, egg laying and viability.

The Zn(2+)-chelating metalloprotease inhibitor 1,10-phenanthroline (phenanthroline, 5-150 microM) elicited dose-dependent contraction of the longitudinal and circular (transverse) musculature of adult male schistosomes. At the same concentrations, phenanthroline did not cause contraction of dispersed individual muscle fibres. The phenanthroline-induced contractions were reduced by the inclusion of 100 or 300 microM Zn2+ in the extracellular medium. Phenanthroline (0.5-150 microM) also inhibited the egg production of adult worm pairs in vitro, with a 98% reduction at 50 microM. When worm pairs were exposed to phenanthroline, the males detached from the dish and released the females, resulting in unpaired worms. At the higher concentrations (50 and 150 microM), the worms were killed in vitro. Worm burdens were reduced by over 50% in infected mice injected with phenanthroline (20 mg/kg/day for 4 days), but twice the dose resulted in only a 25% reduction. Phenanthroline injections also induced an hepatic shift and an unpairing of adult worms in infected mice, and the female worms appeared degenerate and lacked gut pigmentation. Mice fed a diet containing 0.3% phenanthroline received significant protection from infection when challenged with schistosome cercaria, where phenanthroline-fed mice had 94% fewer adult worms than control mice. The broad range of phenanthroline effects on schistosomes suggests broad and important functions for metalloproteases in these worms.

Animals↗

PubMed1998

Indomethacin attenuates oxytocin and hypothalamic-pituitary-adrenal axis responses to systemic interleukin-1 beta.

Systemic administration of the cytokine IL-1 beta produces a significant release of ACTH into the plasma and activation of hypothalamic oxytocin (OT) and corticotropin releasing factor (CRF) cells. However, the mechanism(s) by which systemic IL-1 beta induces these responses is not clear. In the present study, we have investigated the proposal that catecholamine cells of the ventrolateral medulla (VLM) and nucleus of the solitary tract (NTS) can relay circulating IL-1 signals via a prostaglandin-dependent mechanism to effect the HPA axis responses in the rat. Intra-arterial administration of IL-1 beta (1 pg/kg) to otherwise untreated animals produced a prominent release of ACTH into the plasma, substantial c-fos expression in paraventricular medial parvocellular (mPVN) corticotropin releasing factor (CRF) cells, supraoptic (SON) and paraventricular nucleus (PVN) OT cells, area postrema cells, NTS and VLM catecholamine cells and cells of the central amygdala. Pretreatment with the prostaglandin synthesis inhibitor, indomethacin (10 mg/kg body weight ia) 15 min before IL-1 beta administration (1 pg/kg ia) significantly reduced plasma ACTH release and c-fos expression in PVN and SON OT cells and MPVN CRF cells, in addition, the area postrema, A1 and C1 catecholamine cell groups of the VLM and A2 and C2 catecholamine cell groups of the NTS, all exhibited concomitant reductions in c-fos expression. Conversely indomethacin administration did not alter the IL1 beta-induced expression of c-fos in the central amygdala. These data suggest that central pathways involved in the IL-1 beta-induced activation of the HPA axis and OT cells are, at least in part, dependent upon prostaglandin synthesis. It is proposed that neurons in the area postrema, NTS and VLM might mediate this IL-1 beta-induced activation of hypothalamic CRF and OT cells and release of ACTH into the plasma.

Adrenal Glands↗

PubMed1998

Management of substernal goiter.

OBJECTIVE: To analyze the presentation, evaluation and treatment of patients with large substernal goiters, with emphasis on the radiographic evaluation and the results of treatment. STUDY DESIGN: A retrospective chart review of 150 patients undergoing thyroidectomy at the Vanderbilt University Department of Otolaryngology-Head and Neck Surgery. METHODS: Charts of patients undergoing thyroidectomy were reviewed. Those with substernal goiter, defined as a major portion of the goiter within the mediastinum, were included in the study. When available, the radiographic studies were reviewed by a staff neuroradiologist. RESULTS: Twenty-three patients (15.3%) presented with substernal extension of the goiter. Characteristics of these patients included mean age of 59 years, 78% female, symptoms of compression such as dyspnea, choking, and dysphagia (65%), hoarseness (43%), and previous thyroid surgery (30%). Seventeen percent were asymptomatic. Preoperative radiographs demonstrated tracheal compression (73%), tracheal deviation (77%), esophageal compression (27%), and major vessel displacement (50%). Histology revealed multinodular goiter (16/23, 70%), thyroiditis (3/23, 13%), and malignancy (4/23, 17%). The average size of the resected specimen in greatest dimension was 8.0 cm (range, 3.0-14.0 cm) and weighed 148 g (range, 39-426 g). All were successfully approached through a transcervical incision without the need for sternotomy, and total thyroidectomy was performed in 83% of the cases. No major complications have been documented, and no evidence of tracheomalacia was encountered. CONCLUSION: Despite the large size of these goiters and the significant involvement of the major mediastinal structures, all were approached through the transcervical incision. Further, despite significant tracheal involvement, there were no cases of tracheomalacia or major complications. For intraoperative planning, the authors advocate the routine use of preoperative computed tomography scanning.

Adult↗

PubMed1998

Management of frontal sinus fractures with posterior table involvement: a retrospective study.

Management of frontal sinus fracture has been a matter of debate. Combined fractures of the anterior and posterior walls have been managed by various techniques, including observation, open reduction and internal fixation, ablation, obliteration, and, most recently, cranialization. The earlier techniques have met with frequent complications, including sinusitis, mucopyocele, cerebrospinal fluid leak, meningitis, and brain abscess, along with various chronic pain symptoms. Cranialization of the frontal sinus was first introduced for injuries of both walls with intracranial penetration. From 1990 to 1996, frontal sinus fractures of 11 patients (10 men and 1 woman) were treated using the cranialization procedure. Based on patient history, clinical findings, radiographic diagnoses, operative techniques, and follow-ups of these patients the authors conclude that cranialization of the frontal sinus is a safe and effective method of treating posterior table frontal sinus fractures.

Accidents, Traffic↗

PubMed1997

Structure-activity relationships of FMRFamide-related peptides contracting Schistosoma mansoni muscle.

This study reports the potent myoactivity of flatworm FMRFamide-related peptides (FaRPs) on isolated muscle fibers of the human blood fluke, Schistosoma mansoni. The turbellarian peptides YIRFamide (EC50 4 eta M), GYIRFamide (EC50 1 eta M), and RYIRFamide (EC50 7 eta M), all induced muscle contraction more potently than the cestode FaRP GNFFRFamide (EC50 500 eta M). Using a series of synthetic analogs of the flatworm peptides YIRFamide, GYIRFamide and RYIRFamide, the structure-activity relationships of the muscle FaRP receptor were examined. With a few exceptions, each residue in YIRFamide is important in the maintenance of its myoactivity. Alanine scans resulted in peptides that were inactive (Ala1, Ala2, Ala3 and Ala4 YIRFamide; Ala4 and Ala5 RYIRFamide) or had much reduced potencies (Ala1, Ala2 and Ala3 RYIRFamide). Substitution of the N-terminal (Tyr1) residue of YIRFamide with the non-aromatic residues Thr or Arg produced analogs with greatly reduced potency. Replacement of the N-terminal Tyr with aromatic amino acids resulted in myoactive peptides (FIRFamide, EC50 100 eta M; WIRFamide, EC50 0.5 eta M). The activity of YIRFamide analogs which possessed a Leu2, Phe2 or Met2 residue (EC50's 10, 1 and 3 eta M, respectively) instead of Ile2 was not significantly altered, whereas, YVRFamide had a greatly reduced (EC50 200 eta M) activity. Replacement of the Phe4 with a Tyr4 (YIRYamide) also greatly lowered potency. Truncated analogs were either inactive (FRFamide, YRFamide, HRFamide, RFamide, Famide) or had very low potency (IRFamide and MRFamide), with the exception of nLRFamide (EC50 20 eta M). YIRF free acid was inactive. In summary, these data show the general structural requirements of this schistosome muscle FaRP receptor to be similar, but not identical, to those of previously characterized molluscan FaRP receptors.

Amino Acid Sequence↗

PubMed1997

Physiological effects of platyhelminth FMRF amide-related peptides (FaRPs) on the motility of the monogenean Diclidophora merlangi.

The actions of known platyhelminth FaRPs on the contractility of whole-worm preparations of the monogenean, Diclidophora merlangi have been examined in vitro for the first time. All of the peptides tested had excitatory effects on the motor activity of the worm. The order of potency for the peptides tested was: YIRFamide > GYIRFamide = RYIRFamide > GNFFRFamide = FLRFamide. However, although YIRFamide was more potent than GYIRFamide, the latter was the most efficacious on each of the motility parameters (tension, contraction amplitude and contraction frequency) examined at concentrations > or = 0.1 microM. Serotonin, which stimulates contractility in the worm was used as a positive control. The excitatory activity of turbellarian and cestode neuropeptides on a monogenean indicates at least some structural similarities in the neuropeptide receptors of these classes of flatworm.

Animals↗

PubMed1997

Production of cloned lambs from an established embryonic cell line: a comparison between in vivo- and in vitro-matured cytoplasts.

Nuclear transfer procedures were used to determine the in vivo developmental potential of an ovine embryonic cell line isolated from the inner cell mass of a Day 8 blastocyst-stage embryo. This cell line possessed a differentiated epithelial-like cell morphology. In this study, a comparison was made between in vivo- and in vitro-derived oocytes used as recipient cytoplasts in the nuclear transfer procedure. Cultured cells were induced to quiesce and enter presumptive G0 before being used as donor karyoplasts between passages 8 and 16 of culture. After cell fusion, reconstructed embryos were cultured for 6 days in vitro in embryo culture medium. Blastocyst-stage embryos were subsequently transferred to synchronized recipient ewes (n = 37), and development was allowed to proceed to term. There was a significant effect of source of recipient cytoplast, with development being consistently greater with in vivo compared to in vitro cytoplasts in terms of, respectively, blastocysts produced (24.2 +/- 3.8% vs. 17.1 +/- 2.3%; p = 0.1), Day 35 pregnancy rate (40.0% vs. 9.1 %; p < 0.05), and Day 35 embryo survival (19.4% vs. 4.5%; p < 0.05). A high proportion of fetuses died during late gestation (5 of 8). The major abnormalities were associated with the urogenital tract. However, three lambs were delivered alive following cesarean section on Day 147. One lamb, derived from an in vitro-matured oocyte, died after 10 min, while the remaining two from in vivo-ovulated oocytes are apparently normal and healthy. DNA microsatellite markers conclusively show that the three lambs are genetically identical and were derived from the embryonic cell line. In conclusion, some cells from this blastocyst-derived embryonic cell line are totipotent by nuclear transfer and can produce viable offspring.

Animals↗

PubMed1997

Posterior glottic stenosis mechanism and surgical management.

Posterior glottic stenosis with arytenoid fixation is an uncommon complication of laryngeal injury. Though etiologies vary; the most common is prolonged intubation. Patients with this problem are tracheotomy dependent and have compromised voice production. There has been no acceptable approach to reconstruction of the larynx, the majority of patients being treated with some type of vocal fold lateralization. The success rate with this approach varies, and this procedure does not take advantage of the intact neuromuscular status of the larynx. Over the past 3 years we have utilized an alternative approach, to repair the stenosis and mobilize the arytenoids in 10 patients. Our surgical technique involves laryngeal exposure via a laryngofissure, the removal of posterior glottic cicatricial tissues, and the application of an autologous graft. Subsequently, all but one of the patients were able to be decannulated. Subjective postoperative voice analysis showed improved voice production. The pathophysiology for this disorder and a review of different treatment modalities are discussed.

Adolescent↗

PubMed1996

Schistosoma mansoni: L-glutamate-induced contractions in isolated muscle fibers; evidence for a glutamate transporter.

Schistosoma mansoni muscle fibers contract in response to L-glutamate in a dose-dependent manner (10(-6)-10(-3) M). L-aspartate and D-aspartate are likewise effective in eliciting contraction of the fibers. Mammalian glutamate receptor agonists produce little or no contraction at concentrations as high as 1 mM. In addition, common glutamate receptor antagonists do not inhibit the contraction induced by L-glutamate. However, amino acids known to be substrates for the high-affinity glutamate transporter elicit contraction of the muscle fibers. These results suggests that there is a high-affinity glutamate transporter on the muscle fibers which, because of its electrogenic nature, is causing depolarization and contraction. This is supported by the evidence that contraction induced by L-glutamate is dependent on extracellular Ca2+ and is blocked by nicardipine (10 microM). [3H]L-glutamate is taken up in a dose-dependent manner by the muscle fiber preparation. This uptake is also time- and temperature-dependent. Both the L-glutamate-induced contractile response and [3H]L-glutamate uptake are Na(+)-dependent and can be blocked by specific inhibitors of the high-affinity transporter. This experimental evidence supports the hypothesis that there is a Na(+)-dependent high-affinity glutamate transporter on the schistosome muscle membrane.

ATP-Binding Cassette Transporters↗

PubMed1996

Central noradrenergic neurons signal via ATP to elicit vasopressin responses to haemorrhage.

It is now clear that ATP acts as a neurotransmitter in both the peripheral and central nervous systems. In the periphery, purinergic transmission has been best studied at certain sympathetic neuroeffector junctions where ATP, co-localized with noradrenaline, is used to elicit the primary post-junctional response. More recently, several groups have raised the possibility that central catecholaminergic neurons might use ATP in a similar fashion. Accordingly, we now present findings from immediate early gene expression and electrophysiological studies which indicate that ATP, acting through P2 purinoreceptors, is used as a transmitter by caudal brainstem noradrenergic neurons, the A1 group, in their interaction with vasopressinergic neurosecretory cells. Supraoptic nucleus vasopressin cell responses to moderate haemorrhage, known to be generated by the A1 projection, were suppressed by hypothalamic application of the P2 receptor antagonist suramin. However, suramin did not alter vasopressin cell responses to osmotic challenge or severely hypotensive haemorrhage, two stimuli known to excite vasopressin cells independently of the A1 projection. These data are consistent with an identity of action between the A1 input to vasopressin cells and the activation of ATP receptors on vasopressin cells. The use of ATP as a transmitter by other catecholamine neurons in the brain awaits further confirmation, but the present findings suggest that in certain instances the therapeutic manipulation of central catecholamine neuron output might best be achieved with pharmacological agents which target purinergic rather than adrenergic transmission.

Adenosine Triphosphate↗

PubMed1996

Cholinergic inhibition of muscle fibres isolated from Schistosoma mansoni (Trematoda:Digenea).

Cholinergic compounds inhibit FMRFamide-induced contractions in dispersed muscle fibres isolated from adult Schistosoma mansoni. Acetylcholine (ACh) was the most effective cholinergic agonist tested with an EC50 < 100 nM. Less effective were propionylcholine and arecoline with EC50 < 1 microM and butyrylcholine and carbachol with EC50 < 10 microM. Choline, muscarine, pilocarpine, nicotine, DMPP (1,1-dimethylphenylpiperazine) and levamisole were all ineffective. Amongst tested antagonists, d-tubocurarine (100 microM), mecamylamine (1 mM), scopolamine (1 mM) and quinuclidinyl benzilate (10 microM) were all ineffective. Bicuculline, picrotoxin and strychnine were also ineffective. However alpha-bungarotoxin, at 100 nM, was able to block the inhibitory ACh effect. From these data it appears that the cholinergic receptor on the schistosome muscle fibres may be of the nicotinic type, but that its pharmacology is different from that of nicotinic receptors of vertebrates as well as of nematodes or a variety of other invertebrates.

Acetylcholine↗

PubMed1996

Neuromuscular physiology and pharmacology of parasitic flatworms.

The trematode and cestode flatworms include numerous parasitic forms of major medical and economic importance. A better knowledge of the neuromuscular physiology of these animals could lead to development of new control measures against these parasites. Since these animals are near the stem from which all other animals have evolved, better knowledge of these animals could also yield valuable information about the early evolution of nerve and muscle systems in the animal kingdom. This review focuses on what is known about the characteristics of the somatic muscle in these animals. The anatomy of the muscles is described along with a review of current information about their electrophysiology, including descriptions of the ion channels present. Also included is a summary of recently acquired data concerning the nature of serotonin, peptide, acetylcholine and glutamate receptors on the membranes of the muscles.

Animals↗

PubMed1996

Involvement of medullary catecholamine cells in neuroendocrine responses to systemic cholecystokinin.

Systemic administration of cholecystokinin (CCK) stimulates neurosecretory oxytocin (OT) and tuberoinfundibular corticotrophin releasing factor (CRF) cells of the hypothalamus. Data from previous studies suggest that A2 noradrengeric neurons of the dorsomedial medulla contribute to the OT cell response, but the role of other medullary catecholamine cells remains unclear. Using c-fos expression as a marker for cellular activity, we have found that CCK (100 micrograms/kg, i.p.) activates substantial populations of tyrosine hydroxylase and phenyl-N-methyl-transferase immunoreactive cells in the medulla, consistent with recruitment of overlapped noradrenergic and adrenergic cell populations in both the ventrolateral and dorsomedial medulla. In the ventrolateral medulla there was a particularly prominent activation of C1 adrenergic neurons at the level of the obex. To directly test the contribution of VLM catecholamine cells to hypothalamic neuroendocrine cell responses to CCK, animals were prepared with unilateral VLM lesions corresponding to those areas that had displayed the most marked response to CCK. VLM lesioned animals treated with CCK displayed a significant although small reduction in paraventricular nucleus (PVN) OT cell c-fos expression ipsilateral to the lesion, but no change in the responses of supraoptic nucleus OT cells or in cells of the medial parvocellular PVN, many of which are CRF cells. These findings indicate that VLM catecholamine cells make little contribution to hypothalamic neuroendocrine cell responses to CCK and thus serve to further highlight the role of dorsomedial catecholamine cells. However, it is now apparent that, in addition to A2 noradrenergic cells, CCK treatment also recruits C2 adrenergic cells of the dorsomedial medulla, many of which have previously been shown to project to the PVN.

Animals↗