Biomedical subjects

C F Ferris

Publications and source records attributed to C F Ferris.

85 records · Page 5Linked to original sources

PubMed1985

Release and degradation of neurotensin during perfusion of rat small intestine with lipid.

The levels of neurotensin (NT) and its metabolite, the N-terminal octapeptide (NT1-8), identified by HPLC and measured by RIA, were increased in the hepatic-portal circulation of the anesthetized rat during perfusion of the small intestine with a lipid solution, while levels of both peptides remained unchanged in the general circulation. There was no significant arteriovenous difference for NT or NT1-8 during saline perfusion of the small intestine. Plasma collected from the superior mesenteric vein during the infusion of [3H]NT into the superior mesenteric artery showed major peaks of radioactivity with the retention times of NT1-8 and NT1-11 on HPLC. Only 12% of the radioactivity recovered from plasma was intact NT. These studies demonstrate that chromatographically identified NT and its metabolite, NT1-8, are elevated in the portal circulation but not systemic circulation during lipid perfusion and that the small intestine may be both the site of release and metabolism of NT.

Animals↗

PubMed1985

Alcohol and fatty acid stimulation of neurotensin release from rat small intestine.

We have previously reported that neurotensin (NT) is released from the small intestine and elevated in the hepatic-portal circulation in response to the perfusion of the small intestine with a micellar solution of oleic acid. In order to determine the minimum acyl chain length and whether the presence of a carboxylic acid is necessary for the stimulation of NT release, the small intestine of anesthetized rats was perfused with test solutions of fatty acids of 2-, 4-, 8-, or 18-carbons or fatty alcohols of 2-, 4-, or 8-carbons at a concentration of 1 mM prepared in 2.4 mM taurodeoxycholate in 0.9% NaCl. Blood samples, collected from the superior mesenteric vein immediately before the start of the test perfusion and at 15-min intervals thereafter, were extracted immediately and radioimmunoassayed for NT-like immunoreactivity (NTLI) with a C-terminal-directed antiserum. Perfusions of fatty acids with 4 or more carbons and alcohols of 2 or more carbons resulted in a significant elevation (P less than 0.05) in plasma levels of NTLI above the values obtained before the onset of perfusion. Perfusions with ethanol resulted in a value of 4.3 +/- 0.03 mg/dl (SEM) in blood from the superior mesenteric vein while there was no increase in ethanol levels in the peripheral circulation. Perfusion with taurodeoxycholate and 0.9% NaCl alone had no significant effect on plasma levels of the NTLI. In order to characterize the chemical nature of the elevated NTLI, plasma samples from animals perfused with test solution were collected, extracted, pooled, and subjected to HPLC. NT and its N-terminal metabolite, NT(1-8), were quantitated. NT was defined as material having the same retention time as synthetic NT standard and having comparable measurements using N- and C-terminal-directed antisera. Perfusions of fatty acids of four or more carbons and alcohols of two or more carbons resulted in a 2- to 4-fold increase of both NT and NT(1-8) levels in plasma. It is particularly interesting that perfusion with ethanol (2-carbons) causes an elevation in plasma NT, because perfusion with acetic acid (2-carbons) does not increase NTLI. The fact that perfusion of ethanol is effective in releasing intestinal NT suggests that NT may mediate some of the biological effects observed after the consumption of alcohol.

Acetates↗

PubMed1984

Neuropeptide Y: role in light-dark cycle entrainment of hamster circadian rhythms.

Microinjection of neuropeptide Y (NPY) into the suprachiasmatic region of the hypothalamus (SCN) phase shifted the circadian activity rhythm of hamsters housed in constant light. NPY advanced the phase when injected during the 12 h that preceded the daily onset of activity and tended to phase delay the activity cycle when injected during the 12 h after activity onset. In contrast, injection of saline into the SCN or NPY into the ventricular system had no effect on circadian phase. These and other data suggest that NPY functions as a chemical messenger important for the light-dark cycle entrainment of circadian rhythms.

Animals↗

PubMed1984

Vasopressin injected into the hypothalamus triggers a stereotypic behavior in golden hamsters.

Microinjection of arginine vasopressin into the medial preoptic area of the hypothalamus of male and female golden hamsters triggered a complex, stereotypic behavior--flank marking--a type of scent marking used in olfactory communication. The flank marking was not elicited by saline, oxytocin, neurotensin, or angiotensin II. Vasopressin was ineffective when injected into other areas of the hypothalamus or into the lateral cerebroventricle.

Angiotensin II↗

PubMed1984

Avian pancreatic polypeptide phase shifts hamster circadian rhythms when microinjected into the suprachiasmatic region.

The suprachiasmatic nucleus has been identified tentatively as a circadian pacemaker. To examine the functional role of peptides found within suprachiasmatic neurons, avian pancreatic polypeptide and vasopressin were microinjected into the suprachiasmatic region. Avian pancreatic polypeptide, but not vasopressin, shifted the phase of the wheelrunning rhythm as a function of the time of its injection within the circadian cycle. Avian pancreatic polypeptide or a similar peptide may be one component of the neurochemical processes underlying entrainment to the light-dark cycle.

Animals↗

PubMed1984

Stimulation of luteinizing hormone release after stereotaxic microinjection of neurotensin into the medial preoptic area of rats.

Neurons immunoreactive to luteinizing hormone-releasing hormone (LHRH) are localized to the medial preoptico-septal region of the rat hypothalamus, an area known to be essential for the regulation of the surge of luteinizing hormone (LH) that precedes ovulation. The effect of neurotensin (NT) on circulating LH levels following its discrete microinjection into this region was evaluated. Within 30 min after the stereotaxic microinjection of 40 ng of NT in 50 nl into the medial preoptic area (MPOA) just rostral to the organum vasculosum of the lamina terminalis in ovariectomized (OVX), anesthetized rats, plasma LH levels rose from 417 +/- 36 to 923 +/- 113 ng/ml (p less than 0.001). There was also a significant increase (p less than 0.001) in plasma LH levels following the microinjection of 50 ng of norepinephrine in 50 nl in this same site. Similarly, levels of LH increased from 48 +/- 7 to 110 +/- 19 ng/ml (p less than 0.004) following the microinjection of NT into the rostral MPOA on the morning of proestrus in anesthetized rats. In contrast, saline, substance P, leu-enkephalin and LHRH microinjected in the rostral MPOA of OVX rats had no significant effect on circulating levels of LH. The microinjection of NT 0.4 mm rostral or caudal to this area was also without effect. The presence of two binding sites with KdS of 4.2 and 29 nM and site concentrations of 0.11 and 0.68 pmol/mg in tissue homogenates of the rostral MPOA were also established. These data suggest a role for NT in the central regulation of LH release.

Animals↗

PubMed1983

Isolation, biological and chemical characterization, and synthesis of a neurotensin-related hexapeptide from chicken intestine.

A new biologically active peptide of the neurotensin (NT) family, shown previously to cross-react in a COOH-terminal-directed radioimmunoassay for bovine NT, has been isolated from extracts of chicken intestine and identified as H-Lys-Asn-Pro-Tyr-Ile-Leu-OH, which is identical with the biologically active COOH-terminal half of NT except for the amino acid substitutions Lys/Arg and Asn/Arg. It is proposed that this peptide be referred to as Lys8, Asn9, NT8-13 (LANT-6). Synthetic material prepared with this amino acid sequence using the Merrifield technique was immunochemically, chromatographically, and biologically indistinguishable from the native peptide. In contrast to chicken NT which induced hypotension, hyperglycemia, increased vascular permeability, and cyanosis when injected intravenously into anesthetized rats, synthetic LANT-6 brought about primarily a hypertensive response and had little ability to promote hyperglycemia, increased vascular permeability, and cyanosis. In rats pretreated with the alpha-blocker phentolamine and in adrenalectomized rats, the hypertensive response to LANT-6 was blocked, suggesting that adrenal catecholamines mediated this effect. These findings suggest that LANT-6, a natural variant of NT with a different spectrum of biologic activity, may be a NT-related messenger peptide with a different function(s).

Animals↗

PubMed1981

Elevation of plasma neurotensin during lipid perfusion of rat small intestine.

Perfusion of the small intestine with a lipid solution results in elevated plasma neurotensin-like immunoreactivity in blood collected from the superior mesenteric vein. Perfusion of amino acids, glucose, hyperosmotic saline, acidified saline, bile salt and diluted rat bile had no effect. Neurotensin-like immunoreactivity in portal plasma was significantly higher than that measured concomitantly in peripheral arterial plasma. Neurotensin, as identified by high pressure liquid chromatography, rose from 4 to 9 fm/ml (n = 4) and 9 to 18 fm/ml (n = 9) extracted plasma during lipid stimulation as compared to the saline control. These results demonstrate that intraintestinal lipid is an effective and specific stimulus for the release of neurotensin from the small intestine into the portal circulation. However, until a target organ can be shown to respond to these modest levels of plasma neurotensin, it is unsettled whether the peptide is a hormone or whether its elevation in plasma is due to "overflow" of a paracrine agent.

Animals↗

PubMed1981

A functional analysis of dopaminergic innervation of the neurohypophysis.

Dopaminergic neurons arising from cell bodies in the rostral arcuate nucleus of the hypothalamus have been shown to make axoaxonic contact with neurohypophyseal neurosecretory axons. In this study, electrical stimulation of the rostral arcuate nucleus depresses multiunit electrical activity recorded from neurosecretory axons within the neurohypophysis. After a single 5-s stimulus train, neurohypophyseal electrical activity is reduced to 6% of control. The superfusion of dopamine (5 micrograms/microliters) onto the neurohypophysis also has an inhibitory effect. Superfusion directly onto the neurohypophysis of the dopamine-receptor antagonist, pimozide (1 micrograms/microliters), abolishes the inhibitory effect of arcuate nucleus stimulation. These findings suggest that the dopaminergic innervation of the neurohypophysis may have an inhibitory influence on the release of neurohypophyseal hormones.

Animals↗

PubMedDate not supplied

Serotonin blocks vasopressin-facilitated offensive aggression: interactions within the ventrolateral hypothalamus of golden hamsters.

In golden hamsters, vasopressin (AVP) microinjected within the ventrolateral hypothalamus (VLH) facilitates offensive aggression. As serotonin is known to inhibit offensive aggression, we decided to test whether AVP-facilitated behavior is also inhibited by serotonin treatment. Testosterone-treated male golden hamsters received IP injections of fluoxetine, a serotonin reuptake inhibitor, or vehicle 1 h prior to AVP microinjections within the VLH. The animals were tested for offensive aggression in a resident-intruder model after the microinjections, and the results were compared between groups. Pretreatment with fluoxetine inhibited AVP-facilitated offensive aggression. Only one out of nine fluoxetine-treated animals attacked and bit the intruders, compared to six out of seven vehicle-treated animals. Furthermore, we also confirmed by in vitro autoradiography that the VLH contains vasopressin V(1) and serotonin 5-HT1B receptors. Therefore, it is possible that serotonin may inhibit AVP-facilitated offensive aggression by acting directly at the level of the VLH as well as at other sites.

Aggression↗

PubMedDate not supplied

The stability and metabolism of intravenously administered neurotensin in the rat.

The clearance and metabolism of synthetic and tritiated (3H) neurotensin (NT) were studied following its intravenous injection in a pharmacologic dose (500 pmol/kg) into anesthesized rats. Immunoreactive NT (iNT), measured in a radioimmunoassay (RIA) with use of a carboxyl-(C)-terminal directed antiserum, displayed an apparent half-life (t 1/2) of 0.55 min, while that measured by an amino-(N)-terminal directed antiserum had a t 1/2 of 5 min. The radiolabel from injected 3H-NT (3H on Tyr3,11) had a t 1/2 of 6.5 min. High-pressure liquid chromatography of extracts of plasma obtained from the circulation 0.5-3 min after injection of NT and 3H-NT showed the presence of NT and the generation mainly of the fragments NT1-8, NT1-11, and NT9-13, as well as free 3H-labeled tyrosine. The apparent half-lives of intravenously injected synthetic NT1-8, NT1-11 and NT1-12 measured with the N-terminal RIA were 9, 5 and 5 min, respectively, while that for NT9-13 was less than 0.5 min. These results indicate that exogenously injected NT is rapidly metabolized to form N-terminal fragments which are cleared more slowly than NT. These findings suggest that use of N-terminal antisera to detect the release of endogenous NT into the circulation is likely to yield measurements of the fragments NT1-8 and NT1-11 which thus far have been found to be biologically inactive.

Animals↗

PubMedDate not supplied

Inhibition of neurotensin release by a cyclic hexapeptide analog of somatostatin.

Studies were performed to determine whether the cyclic hexapeptide analog of somatostatin, cyclo(N-Me-Ala-Tyr-D-Trp-Lys-Val-Phe) II, could alter circulating levels of neurotensin (NT) and inhibit the release of NT from small intestine following the intraluminal perfusion of lipid and ETOH. The small intestine of anesthetized rats was perfused with 0.9% NaCl, 1mM ETOH, 100 mM ETOH or 1 mM oleic acid with and without the intravenous infusion of the somatostatin analog. Plasma samples collected from the superior mesenteric vein were extracted, chromatographed on HPLC and assayed with both C-terminal and N-terminal antisera to NT. The basal circulating levels of chromatographically and immunochemically identified NT observed during the perfusion of the small intestine with 0.9% NaCl were significantly lower (p less than 0.01) during the IV infusion of the somatostatin analog as compared to animals infused IV with saline. The 2-3 fold increase in plasma levels of NT observed with the intestinal perfusion of oleic acid and ETOH did not occur in animals simultaneously infused IV with the somatostatin analog. The somatostatin analog was also effective in decreasing the basal levels of NT metabolite NT(1-8) as well as inhibiting the increase in this metabolite that accompanies the stimulated release of NT.

Animals↗

PubMedDate not supplied

Plasma levels of human neurotensin: methodological and physiological considerations.

The ingestion of a meal high in fat content is known to increase circulating levels of neurotensin (NT) in humans. However, the magnitude of the postprandial rise of NT in the general circulation and its physiological significance have been subject of much debate. The present study examines circulating levels of NT in male volunteers prior to and following each of their three daily meals (ca. 31 g fat/meal). The response observed are also compared to that elicited by the direct instillation of intralipid (ca. 44 g fat) into the duodenum. NT levels were determined by radioimmunoassay of acid/acetone extracted plasma fractionated by high pressure liquid chromatography. Meals caused a significant but modest increase in NT levels, with the largest increment (ca. 4 fmol/ml) occurring after breakfast. In contrast, NT levels increased ca. 20 fmol/ml with intraduodenal instillation of lipid. The meal-stimulated increases in circulating NT measured here are 4- to 5-fold less than those reported by others, the difference most likely reflecting the lesser amount of lipid ingested. Previous studies provided subjects with single meals containing in excess of 120 g of fat; the 30 g of fat ingested by our subjects, ca. 33% of total caloric intake, is near that recommended by the U.S. Senate, Select Committee on Nutritional and Human Needs. These data show that diets with a reasonable fat content have only a modest effect on circulating levels of NT.

Adult↗