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Biomedical subjects

S I Said

Publications and source records attributed to S I Said.

At least 109 records · Page 6Linked to original sources
PubMed1985

Vasoactive intestinal peptide. Relaxant neurotransmitter in tenia coli of the guinea pig.

Two main candidates have been proposed for the role of relaxant neurotransmitter in the intestine: (a) the purine nucleotide, 5'-adenosine triphosphate (ATP) and (b) the neuropeptide, vasoactive intestinal peptide (VIP). The candidacy of VIP is favored by its precise location in nerve fibers that innervate circular smooth muscle and tenia coli. We have used a photoaffinity analog of ATP, 3'-O-(4-Benzoyl)benzoyl ATP, that binds irreversibly to ATP receptors and inactivates them in the presence of light, and a specific VIP antiserum to examine the claims of VIP and ATP as relaxant neurotransmitters in tenia coli of the guinea pig. Both VIP and ATP caused dose-dependent, tetrodotoxin-insensitive relaxation of tenia coli. The effect of ATP was equipotent to that of its stable isostere alpha, beta-methylene ATP and resistant to degradation by adenosine deaminase, indicating interaction of ATP with purinergic-P2 receptors. Photoactivated 3'-O-(4-Benzoyl) benzoyl adenosine triphosphate selectively inhibited relaxation induced by ATP but had no effect on relaxation induced by VIP or by field (i.e., neural) stimulation. Vasoactive intestinal peptide antiserum (final dilution 1:60), on the other hand, inhibited relaxation caused by VIP and by field stimulation but had no effect on relaxation caused by ATP. Neither normal rabbit serum nor preneutralized VIP antiserum had any effect on relaxation induced by ATP, VIP, or field stimulation. Inhibition of neurally induced relaxation by VIP antiserum ranged from 52% +/- 7% (p less than 0.01) at the lowest frequency of stimulation to 15% +/- 4% (p less than 0.01) at the highest frequency, consistent with competitive interaction between antiserum and neurally released VIP. Near-maximal field stimulation at 1 Hz caused an eightfold (800% +/- 49%, p less than 0.01) increase in VIP release into the bathing medium. The results favor VIP (and probably peptide histidine isoleucine, a relaxant homologue known to be cosynthesized with VIP) as the main neural mediator of relaxation in tenia coli.

Adenosine Triphosphate↗
PubMed1985

[Vasoactive intestinal polypeptide (VIP)--possible importance in diseases of childhood].

Vasoactive intestinal peptide (VIP), first isolated from the gut, was originally considered a candidate gastrointestinal hormone. Since about 1975, however, it has become increasingly clear that it is primarily a neurotransmitter or neuromodulator and that it exerts its functions mainly by local release from nerve endings. VIP plays a hormonal role only when it is released in large amounts from a tumor, with a consequent overflow into the circulation and grossly elevated plasma concentrations of the peptide. Moderately increased VIP plasma and tissue concentrations that cause mainly local effects are found in intestinal ischemia. Crohn's disease and some other chronic inflammatory diseases of the bowel. VIP is also measured in increased amounts in the normal fetus and neonate, where it may play an important physiological role. Such an increase of VIP levels in the circulation could enhance perfusion and metabolic activity of tissues during their rapid-growth period. On the other hand, disorders with a disturbed VIP function such as achalasia and Hirschsprung's disease and possibly also asthma and cystic fibrosis seem to be characterized mainly by a derangement of smooth muscle activity and/or exocrine secretion. Considering this list of disorders where VIP has either a proven or suspected role, it is easy to imagine the significance of this peptide in pediatric pathophysiology.

Asthma↗
PubMed1985

Vasoactive intestinal peptide as a possible transmitter of nonadrenergic, noncholinergic relaxation of pulmonary artery.

Electrical field stimulation of isolated guinea pig pulmonary artery induced a brief initial contraction followed by a more prolonged relaxation. alpha-Adrenergic blockade prevented the contraction and enhanced the relaxation. beta-Adrenergic and cholinergic muscarinic blockade partially reduced the relaxation, but 44.4% of the relaxation persisted after adrenergic and cholinergic blockade. The PA relaxation was associated with the release of immunoreactive VIP, both before and after this blockade. Tetrodotoxin abolished the nonadrenergic, noncholinergic relaxation and markedly reduced the release of VIP. This relaxation was similarly attenuated by a monoclonal antibody against VIP.

Acetylcholine↗
PubMed1985

Vasoactive intestinal polypeptide in cardiac myxoma.

A case of left atrial myxoma is reported in which tumor tissue was found to contain high levels of vasoactive intestinal polypeptide. This finding further supports the concept that myxomas are true neoplasms and may explain some of the poorly understood clinical manifestations of this tumor.

Female↗
PubMed1985

Peptides, endothelium, and pulmonary vascular reactivity.

The lung contains a number of active peptides that can influence endothelial and smooth muscle function. At least two of these peptides are metabolized by endothelium, and endothelium is required for the vasodilator action of several peptides. A vasodilator peptide, VIP, may be the transmitter of the nonadrenergic, noncholinergic system, the major component of neurogenic relaxation of pulmonary vessels.

Endothelium↗
PubMed1984

Effect of vasoactive intestinal peptide on vagally mediated tracheal pouch relaxation.

Vasoactive intestinal peptide (VIP) was studied as a possible neurotransmitter of nonadrenergic inhibition in guinea pig tracheas in vivo, by examining the effects of VIP and isoproterenol on pressure changes induced by nerve stimulation in an isolated, fluid filled, tracheal segment (tracheal pouch). VIP though less potent than isoproterenol produced a dose-dependent relaxation of the pouch. Incubation of the histamine-constricted tracheal pouch with isoproterenol resulted in pouch relaxation and a significant (P less than 0.005) loss of pouch responsiveness to sympathetic nerve stimulation, while non-adrenergically mediated pouch relaxation resulting from vagal stimulation in the presence of atropine was inhibited to a much smaller degree. VIP incubation produced relaxation of the histamine-constricted pouch and resulted in a greater loss of responsiveness to vagal than to sympathetic stimulation (P less than 0.02). By demonstrating loss of vagal responsiveness after VIP in guinea pigs, sympathectomized by 6-hydroxydopamine combined with incubation of the pouch with propranolol to eliminate circulating beta adrenergic inhibition, the effects of VIP incubation on vagally induced pouch relaxation were confirmed to be non-adrenergic in nature.

Animals↗
PubMed1984

Isolation, localization, and characterization of gastrointestinal peptides.

Increasing numbers of peptides have been found in the gastrointestinal tract. Some of these are localized primarily in endocrine cells in the gastrointestinal epithelium (e.g., gastrin, secretin) or pancreatic islets (e.g., insulin, glucagon), and function chiefly as circulating hormones. Other peptides, e.g., VIP, are principally neuropeptides present mainly in nerve cells, nerve fibres and nerve terminals; they function mainly as neurotransmitters or neuromodulators. The isolation of gut peptides has usually depended on the use of characteristic bioassays. More recently, some peptides have been isolated on the basis of unique terminal amino-acid composition. Certain chemical structures are associated with typical biological actions, and several "families" of related peptides are recognized.

Base Sequence↗
PubMed1984

Platelet-activating factor raises airway and vascular pressures and induces edema in lungs perfused with platelet-free solution.

The effects of synthetic platelet-activating factor (PAF) on guinea pig lung were examined in isolated lungs perfused with platelet-free Krebs-Ringer solution. When PAF (1 microgram) was injected into the pulmonary artery (PA), it markedly increased airway pressure (maximal increase, 84.7%) and moderately raised PA pressure (maximal increase, 22.8%). The same dose also provoked a massive (29-fold) release of thromboxane B2 (TXB2), the stable metabolite of TXA2, into the perfusate, beginning before the increases in airway and PA pressures. The concentration of 6 keto-PGF1 alpha, the stable metabolite of prostacyclin, also increased (to 5 times control levels) about 70 s after peak release of TXB2. Indomethacin completely blocked TXB2 release, reduced the magnitude of airway pressure increase by 79%, and shortened its duration, as well as the duration of the PA pressure rise. Larger concentrations of PAF (3 and 10 micrograms) produced even greater increments in airway and PA pressures, but these were only moderately attenuated by indomethacin. Also, PAF increased extravascular lung water, as evidenced by increases in wet/dry lung weight and lung/body weight ratios. In a concentration of 0.1 microgram, PAF had no effects on airway or PA pressures, nor did it stimulate TXB2 or 6-keto-PGF1 alpha release. Lyso-PAF was similarly ineffective. We conclude that PAF induces airway constriction, pulmonary hypertension, and pulmonary edema in guinea pig lung independently of platelets. These effects are associated with stimulated synthesis of TXA2, but the mechanisms of their production remain to be determined.

6-Ketoprostaglandin F1 alpha↗
PubMed1984

Peptides and neurotransmitters that affect renin secretion.

Substance P inhibits renin secretion. This polypeptide is a transmitter in primary afferent neurons and is released from the peripheral as well as the central portions of these neurons. It is present in afferent nerves from the kidneys. Neuropeptide Y, which is a cotransmitter with norepinephrine and epinephrine, is found in sympathetic neurons that are closely associated with and presumably innervate the juxtagolmerular cells. Its effect on renin secretion is unknown, but it produces renal vasoconstriction and natriuresis. Vasoactive intestinal polypeptide (VIP) is a cotransmitter with acetylocholine in cholinergic neurons, and this polypeptide stimulates renin secretion. We cannot find any evidence for its occurence in neurons in the kidneys, but various stimuli increase plasma VIP to levels comparable to those produced by doses of exogenous VIP which stimulated renin secretion. Neostigmine increases plasma VIP and plasma renin activity, and the VIP appears to be responsible for the increase in renin secretion, since the increase is not blocked by renal denervation or propranolol. Stimulation of various areas in the brain produces sympathetically mediated increases in plasma renin activity associated with increases in blood pressure. However, there is pharmacological evidence that the renin response can be separated from the blood pressure response. In anaesthetized dogs, drugs that increase central serotonergic discharge increase renin secretion without increasing blood pressure. In rats, activation of sertonergic neurons in the dorsal raphe nucleus increases renin secretion by a pathway that projects from this nucleus to the ventral hypothalamus, and from there to the kidneys via the sympathetic nervous system. The serotonin releasing drug parachloramphetamine also increases plasma VIP, but VIP does not appear to be the primary mediator of the renin response. There is preliminary evidence that the serotonergic neurons in the dorsal raphe nucleus are part of the pathway by which psychosocial stimuli increase renin secretion.

Animals↗
PubMed1984

[Autonomic nerve innervation of cat pulmonary artery--with special reference to the presence of a non-adrenergic, non-cholinergic inhibitory system].

Electrical field stimulation (EFS), transmural nerve stimulation, was utilized to investigate autonomic nerve innervation of cat pulmonary artery. EFS (duration; 0.8 msec or 1.0 msec, frequency; 20 Hz, voltage; 70 V, for 15 sec) induced small fast constriction followed by large prolonged relaxation on prostaglandin H2 analog-precontracted cat pulmonary arterial strip which was suspended in a 10 ml organ bath. The small fast constriction was blocked or considerably reduced by addition of phenoxybenzamine. The relaxation was partially blocked in some strips by addition of atropine and/or propranolol. Tetrodotoxin or lidocaine not only blocked relaxation which was not blocked by atropine or propranolol, but also farther reduced or completely blocked the relaxation which was partially blocked by atropine and/or propranolol. It is concluded that (1) alpha-adrenergic nerve regulates pulmonary arterial constriction, (2) beta-adrenergic and cholinergic regulations may be present, but their roles may be substantially small and (3) non adrenergic non cholinergic nerve may play major roles in inhibitory regulation of cat pulmonary circulation.

Animals↗
PubMed1984

Vasoactive intestinal peptide relaxes isolated strips of human bronchus, pulmonary artery, and lung parenchyma.

VIP, an endogenous neuropeptide normally present in lungs and other organs, relaxes isolated strips of human bronchus, pulmonary artery, and lung parenchyma in vitro. Pretreatment of these tissues with indomethacin (1 micrograms/ml) markedly enhances the basal tone and the relaxant effect of VIP. The VIP-induced relaxation, especially of pulmonary artery, has a long duration. As a relaxant of human pulmonary arterial strip, VIP is approximately 200 times as potent as prostacyclin, on a molar basis. The results suggest a possible role for VIP as a modulator of airway and pulmonary vascular tone, and as a potential bronchodilator and pulmonary vasodilator in human subjects.

Adult↗
PubMed1984

Vasoactive intestinal polypeptide and acetylcholine are responsible for neurovasodilation in the head of the cat.

There is reason to believe that the dilator innervation to blood vessels of many of the tissues of the head may be part of a common outflow from the central nervous system. Part of the effect of its activation is due to the release of acetylcholine and evidence is presented that, in addition, vasoactive intestinal polypeptide (VIP) release also plays a role. The non-cholinergic part of the dilator response to nerve activity can in a series of blood vessels be correlated with the level of VIP in their wall and is selectively reduced by VIP antiserum. In addition, VIP has suitable characteristics as a vasodilator. Whereas substance P which is present in the walls of many arteries of the head, does not qualify as a putative dilator transmitter. Despite the fact that the physiological role of dilator innervation to the circulation as a whole is not understood, the powerful consequences of the activation of the system in particular blood vessels suggests that this innervation should be seriously considered when studying the regulation of peripheral resistance.

Acetylcholine↗
PubMed1983

Centrally administered VIP increases spindle activity in unanaesthetized rabbits.

The action of VIP on structures responsible for cerebral electrical activity has been investigated in unanesthetized rabbits. VIP was given by slow infusion or bolus into the mesencephalic ventricle or the carotid artery, and topically applied on the motor or visual cortex. Both intracerebroventricular and intracarotid administration induced an increase of spindle activity of the cortex and an inhibition of the strychnine-transmitted spikes. These findings suggest a possible inhibitory role for VIP on certain CNS activity.

Anesthesia↗
PubMed1983

Relaxant action of VIP on cat pulmonary artery: comparison with acetylcholine, isoproterenol, and PGE1.

Vasoactive intestinal peptide (VIP), a potent systemic vasodilator, was recently identified in nerve fibers within the pulmonary arterial wall of cats and other mammals. We have investigated the smooth muscle relaxant action of VIP on isolated strips of kitten pulmonary artery that were placed in a 5-ml bath and precontracted with prostaglandin endoperoxide (PGH2) analogue. The action of VIP was compared with that of acetylcholine, isoproterenol, and prostaglandin E1 (PGE1). The effectiveness of VIP as a relaxant of pulmonary artery, measured as maximal relaxation and expressed in weight equivalents, was 29.9 +/- 2.0 X 10(-2) g in the presence of adrenergic and cholinergic blockers, or 28.8 +/- 4.5 X 10(-2) g in the absence of blockers. This relaxation was similar to that of acetylcholine (30.4 +/- 4.0 X 10(-2) g) and isoproterenol (26.4 +/- 2.2 X 10(-2) g), but smaller than that of PGE1 (41.1 +/- 3.7 X 10(-2) g). Judging by the EC50 or EC10 (effective concentration needed to develop 50 or 10%, respectively, of maximal relaxation), VIP was at least 40 times as potent as acetylcholine, 2,770 times as potent as isoproterenol, and 120 times as potent as PGE1, on a molar basis. The effect of VIP was unaltered in the presence of atropine, propranolol, or phenoxybenzamine in the incubation medium. The findings demonstrate the potent relaxant action of VIP in isolated pulmonary arterial strips and the independence of this action from cholinergic and adrenergic receptors. The results support the possibility that VIP may play an important role in regulating pulmonary vascular tone in kittens.

Acetylcholine↗
PubMed1983

Vasoactive intestinal peptide stimulates renin secretion in vitro: evidence for a direct action of the peptide on the renal juxtaglomerular cells.

The effect of vasoactive intestinal peptide (VIP) and isoproterenol on renin release in vitro was investigated using an isolated superfused rat glomerular preparation. VIP at a dose of 10(-9)-10(-7) M significantly stimulated renin release in a dose-related manner while 10(-10) M was ineffective. These data are consistent with the hypothesis that VIP is a renin-stimulating factor and can have this effect by acting directly on the renal juxtaglomerular cells.

Animals↗
PubMed1983

Histochemical and ultrastructural characterization of serotonin-containing cells in rabbit tracheal epithelium.

Tracheal endocrine cells (TECs) that contain serotonin have been characterized previously by staining with ferric ferricyanide. In the present article, the ferric ferricyanide staining reaction has been used to locate the TECs in deplasticized thick sections of Epon-embedded rabbit tracheas. Adjacent thin sections of the same cell were subsequently observed by electron microscopy. The TECs were filled with dense-core vesicles (DCVs) located in the cytoplasm between the nucleus and the lumen and also lateral to the nucleus. In a separate experiment, pieces of rabbit trachea were treated with a solution of glutaraldehyde-dichromate to demonstrate the presence of amines. High levels of chromium were detected in the DCVs by energy-dispersive X-ray analysis. The results from these studies have correlated the ultrastructure of a serotonin-containing endocrine cell present in rabbit tracheal epithelium with a cell type previously characterized only by light and fluorescence histochemical methods. The results also indicate that serotonin in these cells is stored in the DCVs.

Animals↗