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Biomedical subjects

S I Said

Publications and source records attributed to S I Said.

At least 145 records · Page 8Linked to original sources
PubMed1980

Effect of VIP, phenoxybenzamine and prednisolone on cyclic nucleotide content of isolated guinea-pig lung and trachea.

Vasoactive intestinal polypeptide (VIP) increased the cyclic AMP content of guinea pig lung and tracheal tissues. Combinations of the peptide with prednisolone or with phenoxybenzamine potentiated the effect of VIP on cyclic AMP. The trachea-relaxant effect of VIP also was reinforced by the addition of prednisolone or phenoxybenzamine. At the same time, cyclic GMP content in these tissues changed little in response to these agents. The results provide a biochemical basis for the tracheal-relaxant action of these agents, and for the potentiation of bronchodilation by prednisolone and by alpha-receptor blockade. The findings are also consistent with the view that relaxation of airway smooth muscle is mediated by an elevation of intracellular cyclic AMP.

Animals↗
PubMed1980

Vasoactive intestinal polypeptide (VIP) in mouse and rat brain: an immunocytochemical study.

Immunoperoxidase technique and light microscopy were used to investigate the distribution of vasoactive intestinal polypeptide (VIP) in mouse and rat brain. Both 50 micrometers unmounted cryostat and 6 micrometers deparaffinized sections were studied in coronal or sagittal plane. At least 4 different major VIP systems were found: (1) an intracerebral cortical system; (2) one innervating the central amygdala and nucleus of the stria terminalis; (3) a pathway originating in the suprachiasmatic nucleus of the hypo thalamus; and (4) another originating in the central grey of the midbrain. Specific cell body staining was seen in the limbic and neocortex, in the basal-caudal portion of the suprachiasmatic nucleus of the hypothalamus, and in the central grey of the midbrain. Heavy terminal field patterns were noted in the suprachiasmatic nucleus, central amygdaloid nucleus, bed nucleus of the stria terminalis and nucleus accumbens. Fiber density was moderate in the tuberculum olfactoriu, anterior hypothalamus including the medial preoptic area, mediobasal hypothalamus (especially dorsomedial region), periventricular thalamus, lateral lemniscal system, parabrachial nucleus, nucleus solitarius, and area postrema. Fibers could be traced dorsally from the suprachiasmatic nucleus to the dorsomedial and paraventricular nuclei of the hypothalamus and the periventricular nucleus of the thalamus. Scattered cell bodies and fibers were found in a number of other forebrain and brain stem areas with only a rare fiber seen in median eminence.

Amygdala↗
PubMed1980

The lung in relation to vasoactive polypeptides.

Among the metabolic functions of the lungs are the formation, release, activation and inactivation of biologically active peptides. The following peptides may be present or formed in normal lung: vasoactive intestinal peptide or a peptide closely related to it, a spasmogenic peptide not yet fully identified, bradykinin, substance P, a bombesin-like peptide (especially in fetal and neonatal lung), and eosinophil-chemotactic peptides. These peptides are found in special neuroendocrine cells, in neurons, or in mast cells. Normal lung also inactivates bradykinin and activates angiotensin; both processes are catalysed by the same enzyme (kininase II or angiotensin-converting enzyme), located in pulmonary vascular endothelium. Pulmonary tumours and certain non-tumorous lesions can produce and release a variety of peptide hormones that are not normally generated by the lung in substantial amounts. This 'ectopic' secretion of hormones may be detectable only by sensitive assays or may result in specific clinical syndromes.

Animals↗
PubMed1980

In vitro stimulation of prolactin release by vasoactive intestinal peptide.

The effect of vasoactive intestinal peptide (VIP) on anterior pituitary hormone release was examined in a variety of in vitro preparations. Synthetic VIP was capable of stimulating increased prolactin (PRL) release from male rat hemipituitaries in doses as low as 10-9M only when the enzyme inhibitor bacitracin was present in the incubation medium. Natural porcine VIP was similarly capable of stimulating PRL release, but only at higher doses (10-6M). Additionally, synthetic VIP was capable of stimulating PRL release from dispersed anterior pituitary cells harvested from adult male and lactating female rats and from an enriched population of lactotrophs obtained by unit gravity sedimentation of similar dispersed cells from infantile female rats. No effect of VIP on luteinizing hormone, growth hormone or thyroid stimulating hormone release was seen. These findings taken in concert with the presence of VIP in the hypothalamus, pituitary and hypophyseal portal plasma of the rat suggest a physiological role for VIP in the control of PRL secretion.

Animals↗
PubMed1980

Effect of acetylcholine and vasoactive intestinal peptide on cerebral blood flow.

These experiments were performed to determine whether the neurotransmitters acetylcholine (ACh) and vasoactive intestinal peptide (VIP) increase cerebral blood flow (CBF). In anesthetized dogs, infusion of very large doses of ACh (500 microgram/min) into the carotid artery increased CBF (measured with microspheres) 50%. Anatomical limitations prevented adequate testing of cerebrovascular responses in dogs. In anesthetized rabbits, infusion of ACh (10 microgram/min) into the carotid artery produced a twofold increase in CBF. Vessels in gray matter were more responsive than vessels in white matter. ACh did not alter cerebral oxygen consumption, which indicates that the dilator effect of the drug is not an indirect effect mediated through an increase in metabolism. The vasodilator response to ACh was attenuated by atropine (1 mg iv). Intracarotid infusion of VIP in rabbits increased blood flow to cerebral gray matter: infusion of VIP (10 microgram/min) incresed flow 33%. We conclude that 1) cerebral vasodilator responses to ACh and VIP are larger than previously recognized and 2) responses to these drugs occur primarily in cerebral gray matter. Because the neurotransmitters increase CBF significantly, these studies should encourage further studies concerning effects of cholinergic and peptidergic nerves on cerebral vessels.

Acetylcholine↗
PubMed1980

Mechanism of action of vasoactive intestinal polypeptide on cerebral arterioles.

The effect of vasoactive intestinal polypeptide (VIP) on cerebral arterioles was examined in anesthetized cats equipped with an acutely implanted cranial window for the observation of the pial microcirculation. Topical application of VIP on the surface of the brain in doses of 0.01-1.0 microgram/ml produced a dose-related vasodilation that was of equal magnitude in small (< 100 micrometer diam) and large (> 100 micrometer diam) pial arterioles. The maximum dilation averaged 20% of the control diameter. There were no associated changes in arterial blood pressure or in arterial CO2 tension. In additional experiments the vasodilator effect of VIP was completely inhibited by pretreatment with intravenous indomethacin or AHR-5850. These nonsteroidal anti-inflammatory drugs inhibit cyclooxygenase activity and thereby interfere with the synthesis of prostaglandins and related compounds. The vasodilator effect to topical histamine was unaffected by indomethacin and AHR-5850. The results show that VIP has a strong vasodilator effect on pial arterioles of the cat and suggest that this effect is mediated by prostaglandins.

Animals↗
PubMed1980

Effect of VIP infusion in water and ion transport in the human jejunum.

Infusion of vasoactive intestinal polypeptide (VIP) is known to cause intestinal secretion in animal models. The present study was designed to answer the question whether VIP has a similar effect on the human intestine. Pure porcine VIP was administered by constant i.v. infusion to healthy subjects while their jejunum was perfused with a plasma-like electrolyte solution. At the lowest VIP infusion rate (100 pmol/kg/hr), plasma VIP levels rose two- to four-fold, and there was an increase in the transmucosal potential difference but no change in sodium chloride absorption. At higher VIP infusion rates (200 and 400 pmol/kg/hr), VIP plasma concentrations rose to levels commonly observed in patients with pancreatic cholera syndrome. At these levels VIP caused a dose-dependent decrease of water and sodium absorption. Chloride absorption changed to secretion, while bicarbonate movement remained completely unaffected. Chloride secretion was active, since it occurred against an electrical and chemical gradient. All changes induced by VIP were reversible after discontinuance of VIP infusion. Our observations suggest that elevated levels of circulating VIP are capable of affecting water and ion movement in the human jejunum. They lend support to the hypothesis that high levels of circulating VIP may be a mediator of secretory diarrhea in some patients with pancreatic cholera syndrome.

Adult↗
PubMed1980

Neural release of vasoactive intestinal peptide from the gut.

The release of vasoactive intestinal peptide (VIP) from the canine gut and its possible neural origin were studied using two agents, oxytocin and neostigmine, known to increase peripheral levels of VIP. Oxytocin and neostigmine increased the portal concentrations of VIP by threefold and sevenfold, respectively. A considerable portal/femoral vein gradient ranging from twofold in the basal state to sevenfold during stimulation with neostigmine indicated that the gut was the main source of circulating VIP. The contribution of the brain was minor, and that of the uterus was undetectable. Release of VIP occurred from the entire gut: After enterectomy, the residual gut (stomach, pancreas, and proximal duodenum) released spontaneously a large amount of VIP which masked the effect of oxytocin. Tetrodotoxin and hexamethonium, but not atropine, inhibited oxytocin-stimulted release of VIP by 80% and 60% respectively. This prompted the conclusion that the release of VIP was predominantly neurally mediated and that the chain of transmission involved a preganglionic cholinergic pathway. Hexamethonium strongly inhibited neostigmine-stimulated release of VIP. Atropine was even more potent in that it abolished the effect of neostigmine. The effect of atropine was attributed to a blockade of ganglionic muscarinic receptors, which are preferentially activated by cholinesterase inhibitors like neostigmine. The results of this study and those derived from electrical stimulation of the vagus nerve are consistent with the hypothesis that circulating VIP is released from intrinsic neurons of the gut under preganglionic cholinergic control.

Animals↗
PubMed1979

Axonal transport of vasoactive intestinal peptide in sciatic nerve.

Dense plexuses of neurones containing immunoreactive vasoactive intestinal peptide (VIP) have been found in discrete areas of the central nervous system and in peripheral organs, including the gastrointestinal tract, pancreas and urogenital system. In many of these locations VIP is concentrated in nerve endings, where it can be released by high K+ concentrations in a Ca2+-dependent manner. VIP release may also be provoked by electrical stimulation of nerves, for example the vagus. VIP thus shows some of the features of neurotransmitter or neuromodulator substances. The presence of immunoreactive VIP in the fine terminal varicosities as well as in the cell bodies of neurones suggests that it might be transported from the perikaryon, where it is presumably formed, to the nerve endings, through the axonal transport system. Such transport would be in keeping with a role for the peptide as a neurohumor or neurohormone. We report here that VIP accumulates in constricted rat sciatic nerves in a manner suggesting fast, anterograde axonal flow.

Animals↗
PubMed1979

Vasoactive intestinal polypeptide (VIP) as a mediator of the watery diarrhea syndrome.

Evidence that VIP is the principal humoral mediator of the watery diarrhea syndrome includes: (a) actions of VIP in experimental anaimals parallel the clinical manifestations of the syndrome; (b) infusions of VIP induce watery diarrhea in intestinal loops of dogs and a picture resembling the clinical syndrome in pigs, at circulating levels of the peptide similar to those observed in human disease; (c) most patients with the watery diarrhea syndrome and underlying tumors have elevated plasma levels of VIP; (d) in those patients in whom pre- and postoperative measurements were made, plasma VIP levels fell to the normal range with removal of the tumor and relief of the diarrhea; and (e) extracts of such tumors are rich in VIP-immunoreactivity and VIP-like biologic activity. A few patients with the syndrome have been reported to have normal plasma VIP levels, and it is possible that other humoral agents (such as pancreatic polypeptide, prostaglandins) may contribute to the production of the diarrhea.

Adenocarcinoma↗
PubMed1979

Effects of vasoactive intestinal polypeptide (VIP) on lower esophageal sphincter in awake baboons: comparison with glucagon and secretin.

The effects of vasoactive intestinal polypeptide (VIP), glucagon, and secretin on lower esophageal sphincter pressure were investigated in awake baboons. The three hormones were compared with respect to effect on (1) resting lower esophageal sphincter pressure and (2) maximal stimulatory response to pentagastrin. VIP was shown to reduce resting and pentagastrin-stimulated lower esophageal sphincter pressure with significantly greater potency than either secretin or glucagon. For reduction of resting lower esophageal sphincter pressure, the potency ratio of VIP to secretin was 16:1 and of VIP to glucagon was 32:1 (P less than 0.05). For inhibition of pentagastrin-stimulated sphincter pressure, the potency ratio of VIP to secretin was 32:1 and of VIP to glucagon was 64:1 (P less than 0.02). This demonstration of significantly increased potency of VIP over known inhibitory hormones strengthens the suggestion that VIP may have a physiologic role in the control of lower esophageal sphincter function.

Animals↗
PubMed1979

Radioimmunologic localization of vasoactive intestinal polypeptide in hypothalamic and extrahypothalamic sites in the rat brain.

Using a specific radioimmunoassay (RIA), we have quantitated the hypothalamic and extrahypothalamic distribution of vasoactive intestinal polypeptide (VIP) in the rat brain. Highest concentrations of VIP were found in cerebral cortex, suprachiasmatic nucleus, and medial amygdaloid nucleus. Lower concentrations were found in the anterior hypothalamic area, medial preoptic area, peri- and paraventricular nuclei, and hippocampus. Significant levels of VIP were also found in the anterior pituitary. Very little VIP was detected in median eminence and cerebellar cortex. This distribution of VIP in areas of the rat brain known to be important to neuroendocrine function suggests a role for VIP in the control of anterior pituitary events.

Animals↗