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Biomedical subjects

S Rosell

Publications and source records attributed to S Rosell.

At least 55 records · Page 3Linked to original sources
PubMed1982

Effects of neurotensin on the transit of gastrointestinal contents in the rat.

In this study the influence of neurotensin on gastric emptying, transit of gastrointestinal contents and ileo-cecal emptying was studied in the conscious rat. A bolus of radioactive marker was deposited in the gastrointestinal lumen and was monitored at different time intervals during its passage along the bowel. Gastric emptying was inhibited in a dose-dependent manner by i.v. infusion of 6 and 12 (p less than 0.01) pmol x kg-1 x min-1 of neurotensin. The transit of the gastrointestinal contents was retarded by 3 (p less than 0.001) and 6 (p less than 0.001) pmol x kg-1 x min-1. In addition, at 12 pmol x kg-1 x min-1 the distribution of the radioactivity was spread out and the radioactive front migrated farther. Infusion of 6 pmol x kg-1 x min-1 of neurotensin also produced spreading of the radioactivity in the intestine with proximal pooling and rapid migration of the front of the radioactive bolus (p less than 0.001). Ileo-cecal emptying was inhibited by neurotensin at 6 pmol x kg-1 x min-1, with pooling of the radioactivity proximal to the ileo-cecal valve (p less than 0.001). These data indicate that neurotensin prolongs the transit time of the chyme in the stomach and small intestine. Thus, neurotensin may facilitate thorough digestion of the chyme in the small intestine and enhance the absorption of nutrients.

Animals↗
PubMed1982

Blood flow in human adipose tissue after infusion of (Gln4)-neurotensin.

(Gln4)-neurotensin, 18 pmolXkg-1Xmin-1, was infused i.v. during 20 min in 10 healthy male volunteers. Adipose tissue blood flow was continuously monitored by measuring the disappearance rate of 99mTc-pertechnetate injected s.c. on the abdomen and thigh. Heart rate and blood pressure were measured and calf blood flow studied by venous occlusion plethysmography. Neurotensin-like immunoreactivity (NTLI) in serum was determined. Infusion of isotonic saline served as control. During intravenous infusion of (Gln4)-neurotensin the first order rate constants of 99mTc-pertechnetate from the abdomen decreased by 21.9 +/- 5.9% from a basal value of 8.3 +/- 0.5% min-1 (p less than 0.01). The reduction in blood flow started after a latent period of 5-10 min and persisted throughout the thirty minute observation period following infusion. A significant correlation (r=0.87, p less than 0.001) was found between the percentage decrease in blood flow from abdominal fat and the body fat content of the subjects as determined from the sum of four skinfolds. Blood flow from thigh fat did not change significantly, nor did heart rate, blood pressure or calf blood flow. During infusion of (Gln4)-neurotensin plasma neurotensin-like immunoreactivity (NTLI) increased successively. Ten minutes after starting the infusion the mean plasma NTLI level had increased from 20 +/- 5 pM to 302 +/- 31 pM; at 20 min it was 473 +/- 51 pM. These concentrations are within the range found after eating a fatty meal. The results indicate that neurotensin plays a physiological role in the regulation of human adipose tissue blood flow and may be of importance for the postprandial uptake of substrates in adipose tissue in certain regions. We suggest that neurotensin deserves consideration as an endocrine hormone affecting the regional deposition of fat postprandially.

Adipose Tissue↗
PubMed1982

Antagonism by (D-Pro2, D-Trp7,9)-substance P of the cerebrovascular dilatation induced by substance P.

The effects of (D-Pro2, D-Trp7,9)-substance P, a structural analogue of substance P, were examined in two models on cerebrovascular responses to substance P(SP) in cats; in vitro using segments of the middle cerebral artery and in situ by microapplication of the peptides close to pial arterioles. (D-Pro2, D-Trp7,9)-SP in concentrations up to 6.6 x 10(-6) M was without significant effect upon isolated middle cerebral arteries under normal conditions and in arteries contracted with prostaglandin F2 alpha. SP caused concentration-dependent relaxations of middle cerebral arteries contracted by prostaglandin F2 alpha (mean +/- SE; EC50: 2.0 +/- 1.6 x 10(-9) M). The presence of (D-Pro2, D-Trp7,9)-SP shifted the concentration-response curve of SP towards higher concentrations without significantly effecting the maximum response of the arteries to SP. A relaxation by 24.2 +/- 4.0% (n = 6) was obtained in prostaglandin F2 alpha contracted arteries by increasing the potassium concentration with 2 mM in the buffer solution. This response to potassium was unaltered in the presence of 6.6 x 10(-6)M of (D-Pro2, D-Trp7,9)-SP (25.0 +/- 7.1%, n = 5). Perivascular microapplication of SP around individual pial arterioles in situ effected dose-dependent increases in vascular calibre (mean response 14.5 +/- 2% with SP, 10(-7)M). The concomitant perivascular administration of (D-Pro2, D-Trp7,9)-SP (6.6 x 10(-6)M), which alone did not alter the arteriolar calibre, attenuated significantly the cerebrovascular response to SP (mean response 1.5 +/- 3.2%). On the basis of the agonist-antagonist relation found, these observations point to the possibility of a specific SP receptor site in cerebral arteries and arterioles.

Animals↗
PubMed1982

The effect of intraduodenal installation of oleic acid on plasma neurotensin-like immunoreactivity and on gastric acid secretion stimulated by betazole and sham feeding in man.

Intraduodenal administration of oleic acid has previously been shown to inhibit gastric acid secretion induced by pentagastrin in man. This inhibition was dose-dependent and significantly correlated to a rise in plasma concentration of neurotensin-like immunoractivity (NTLI). Maximal inhibition occurred with a volume of oleic acid of 20 ml. In the present study intraduodenal instillation of 20 ml. of oleic acid inhibited acid secretion evoked by sham feeding in healthy subjects but did not significantly inhibit the near-maximal acid secretion stimulated by the histamine analogue betazole. The inhibition of acid secretion induced by sham feeding was the same (about 45%) as the inhibition of pentagastrin-stimulated secretion. Plasma NTLI rose significantly in both the sham feeding and betazole experiments and peaked at about 145 pM. The results are in agreement with the inhibitory characteristics of neurotensin and support the hypothesis that the inhibition of gastric acid secretion by small amounts of intestinal fat is at least partly mediated by neurotensin.

Adult↗
PubMed1982

Design and synthesis of effective antagonists of substance P.

The agonist/antagonist activities of four background analogs of substance P (SP) facilitated design and synthesis of 12 new analogs to achieve effective antagonists. (D-Pro2, D-Phe7, D-Trp9)-SP, (D-Pro2, D-Trp7,9)-SP and (D-Arg1, D-Phe7, D-Trp9)-SP showed no agonist activity; 9 analogs showed weak agonist activity of SP. (D-Pro2, D-Trp7,9)-SP was the most potent antagonist which at a concentration of 10(-5) required a 3-fold increase in SP to allow a 50% response by SP. (D-Pro2, Lys6, D-Phe7)-SP and (D-Pro2, D-pClPhe7, D-Trp9)-SP were also potent, and the antagonism was competitive. For specific pairs of peptides, Lys6 is a promising substituent. D-Trp7,9 was as effective as Lys6, D-Phe7. D-pClPhe7 was three times as effective as D-Phe7. D-Dln6 was 1.33-fold better than D-Gln5. D-Pro2 and D-Pro4 were equally effective. D-Pro2 was 1.5 times as effective as D-Lys3. D-Pro2 may not be important. D-pClPhe9 and D-Trp9 were equally effective.

Animals↗
PubMed1982

Peripheral and central nervous actions of substance P antagonists.

Studies with the SP-analogues (D-Pro2, D-Phe7, D-Trp9)-SP and (D-Pro2, D-Trp7,9)-SP show that they inhibit the action of SP in a variety of organs both in vitro and in vivo. They also block several non-cholinergic, non-adrenergic effects of nerve activation. Experimental evidence suggest that (D-Pro2, D-Phe7, D-Trp9)-SP and (D-Pro2, D-Trp7,9)-SP are specific SP-antagonists of the competitive type with little or no agonist activity. The present data show that SP-antagonists will be of great importance in clarifying functions of SP.

Animals↗
PubMed1982

(Gln4)-neurotensin changes the motility pattern of the duodenum and proximal jejunum from a fasting-type to a fed-type.

The effect of (Gln4)-neurotensin on the motor activities of the duodenum and small proximal jejunum was investigated in 8 healthy volunteers who fasted for at least 8 h. Motor activity was monitored by measuring the intraluminal pressure at three levels. The proximal site for pressure recording was in the first part of the duodenum, the middle was at the angle of Treitz, and the distal was 25 cm further down. Under control conditions the median time between the migrating motility complexes was 106.3 min. (Gln4)(-Neurotensin, 3 or 6 pmol/kg . min, infused intravenously for 200 min inhibited the migrating motor complexes for 220.4 min (median time) and they were replaced by irregular pressure waves with a frequency of 4-7 waves/min. The plasma concentration of neurotensinlike immunoreactivity increased from 13 +/- 2.8 pM to 131 +/- 6 pM and 231 +/- 16 pM, respectively. Ingestion of fat (55 ml 20% Intralipid) inhibited the migrating motor complex for 196.1 min (median time) and the migrating motor complexes were replaced by irregular pressure waves. The data show that (Gln4)-neurotensin alters the motility pattern in the duodenum and proximal jejunum in man from a fasting- to a fed-type. They further support the contention that neurotensin may function as an endocrine hormone participating in the postprandial regulation of intestinal motility.

Adult↗
PubMed1981

A substance P antagonist, [D-Pro2, D-Trp7,9]SP, inhibits inflammatory responses in the rabbit eye.

Neurogenic factors released by antidromic nerve stimulation are thought to be in part responsible for the vasodilation and breakdown of the blood-aqueous barrier that follows trauma to the eye. Substance P is one candidate for the mediation of the inflammatory response since it is thought to be a neurotransmitter in sensory afferents and since exogenous substance P is capable of eliciting a response characteristic of inflammation. In rabbits, intravitreal or topical application onto the eye of a specific substance P antagonist, [d-Pro2, D-Trp7,9]SP, inhibited not only the irritant effects of exogenous substance P but also the inflammatory response to a standardized trauma (infrared irradiation of the iris). These observations suggest that substance P, or a related peptide, is a neurogenic mediator of the inflammatory response in the eye.

Animals↗
PubMed1981

Effects of neurotensin and neurotensin analogues on the migrating myoelectrical complexes in the small intestine of rats.

The purpose of the present experiments was to study the effect of neurotensin and neurotensin analogues on the migrating myoelectrical complexes in the small intestine of rats. Four bipolar electrodes were implanted into the muscular wall of the small intestine. The electrodes were placed 5, 15, 25 and 35 cm distal to the pylorus. 7-10 days after the operation the animals were fasted for 48 h with free access to water. Some experiments were performed on conscious rats and in others the rats were anesthetized with pentobarbital, 30 mg/kg. I.v. infusion of either neurotensin (NT) or (Gln4)-neurotensin at doses of 1.8, 3.6 and 7.1 pmol X kg-1 X min-1 abolished the migrating myoelectric complexes, which were replaced by increased spiking activity along the whole length of the small intestine from which activity was recorded. The changes in myoelectrical activity were observed within 2-4 min after commencement of the infusion. The activity returned to control levels within 5-15 min after the end of the infusion period. The neurotensin sequences NT 9-13, NT 8-13, NT 4 -13, NT 1-9 and (Gln4)-NT 1-11 did not induce any changes in the electrical activity in the small intestine. The effects of NT and (Gln4)-neurotensin on the myoelectrical activity in the small intestine were indistinguishable. The changes induced by NT or (Gln4)-NT resemble those found after the ingestion of food. The present data indicate that the intact NT sequence, rather than smaller NT fragments, is necessary to induce changes in myoelectrical activity in the small intestine.

Action Potentials↗
PubMed1981

Effects of neurotensin, substance P and methionine-enkephalin on colonic motility.

The influence of neurotensin, substance P and methionine-enkephalin (met-enkephaline) on proximal and distal colonic motility was studied in anesthetized cats. When administered i.v, at a dose of 14 pmol x kg-1 x min-1, neurotensin increased basal smooth muscle tone and antiperistaltic activity in the proximal colon. After higher doses of neurotensin the basal muscle tone also increased in the distal colon. Substance P at a dose of 17 pmol x kg-1 x min-1 selectively and powerfully stimulated the distal colon, thus causing a mass contraction pattern with a concomitant decrease in peristaltic amplitude. In the proximal part of the colon 17 pmol x kg -1 x min-1 of substance P exerted an inhibitory action on the peristaltic amplitude in animals with a high level of spontaneous activity. In addition, the basal muscle tone was slightly decreased. In animals with sluggish spontaneous activity, however, no effects were detected in the proximal colon. With increasing doses of substance P forceful contractions of the proximal colon were also registered. Met-enkephalin at a dose of 40 pmol x kg-1 x min-1 increased the smooth muscle basal tone with no effect on the peristaltic activity in the proximal or distal segments. The effect on basal tone was blocked by naloxone. Thus, neurotensin, substance P and met-enkephalin have distinct motor actions on the colon. At low doses neurotensin may stimulate the churning and mixing functions of the proximal colon. Substance P exerts its major effects on the distal part with a mass contraction response and met-enkepahlin increases the basal muscle tone equally in the proximal and distal parts of the colon.

Animals↗
PubMed1981

Fat inhibition of gastric acid secretion in man and plasma concentrations of neurotensin-like immunoreactivity.

The effects of intraduodenal administration of oleic acid (5, 10, 20, and 40 ml) on gastric acid secretion stimulated by a submaximal intravenous pentagastrin infusion and on plasma concentrations on neurotensin-like plasma immunoreactivity (NTLI) were studied in 18 healthy subjects. Each volume of oleic acid or saline (controls) was tested in six subjects except the volume of 20 ml, which was given to ten subjects. Gastric acid secretion was studied for a 2-h period at 15-min intervals after intraduodenal infusion. Five milliliters oleic acid evoked a significant inhibition (29%) of gastric acid secretion. Maximal inhibition by oleic acid appeared after 20 ml (43%), which was significantly greater than after 10 ml. In seven duodenal ulcer (DU) patients 20 ml oleic acid evoked an inhibition of 20%, which was significantly lower than in the healthy subjects. Proximal gastric vagotomy (PGV) abolished the fat inhibition in DU patients. Basal and peak NTLI concentrations after 20 ml oleic acid were significantly lower in DU patients than in health subjects. In DU patients there was no significant difference in the integrated response of NTLI before and after PGV. The 2-h integrated NTLI response was dependent on the administered volume of oleic acid in healthy subjects. There was a correlation between acid inhibition and the integrated response ot NTLI in healthy subjects. This suggests that immunoreactive neurotensin may be involved in the oleic-acid-induced inhibition of gastric acid secretion. Neurotensin, or a neurotensin metabolite, apparently exerts its inhibitory effect at a synaptic level, which explains the finding that oleic acid did not inhibit gastric acid secretion after PGV. Neurotensin may have a physiological role as a hormone with enterogastrone functions.

Adult↗