GRP nerves in pig antrum: role of GRP in vagal control of gastrin secretion

1987 ◽  
Vol 253 (5) ◽  
pp. G643-G649 ◽  
Author(s):  
J. J. Holst ◽  
S. Knuhtsen ◽  
C. Orskov ◽  
T. Skak-Nielsen ◽  
S. S. Poulsen ◽  
...  
Keyword(s):  
Substance P ◽  
Vagal Stimulation ◽  
Nerve Fibers ◽  
Gastrin Cells ◽  
Gastrin Secretion ◽  
Substance P Antagonist ◽  
Vagal Nerves ◽  
Vagal Innervation ◽  
Dose Dependent

We extracted gastrin-releasing peptide (GRP) and its C-terminal decapeptide corresponding to 6.4 and 6.8 pmol/g from pig antrum mucosa. By immunohistochemistry GRP was localized to mucosal, submucosal, and myenteric nerve fibers. A few nerve cell bodies were also identified. Using isolated perfused pig antrum with intact vagal innervation, we found concomitant, atropine-resistant release of GRP and gastrin during electrical stimulation of the vagal nerves. Intra-arterial GRP at 10(-11)-10(-10) mol/l caused up to fivefold, dose-dependent increases in gastrin secretion; higher doses were less effective and completely desensitized the gastrin cells for the lower doses. After desensitization, vagal stimulation no longer produced gastrin secretion. The substance P antagonist [D-Arg, D-Pro, D-Trp, Leu]-substance P, described as also antagonizing the actions of bombesin, decreased the gastrin response to GRP and abolished the effect of vagal stimulation. The available evidence strongly suggests that GRP nerves are responsible for the stimulatory vagal effects on gastrin secretion in the pig.

GRP-producing nerves control antral somatostatin and gastrin secretion in pigs

1987 ◽  
Vol 253 (6) ◽  
pp. G767-G774 ◽  
Author(s):  
J. J. Holst ◽  
S. Knuhtsen ◽  
C. Orskov ◽  
T. Skak-Nielsen ◽  
S. S. Poulsen ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Substance P ◽  
Nerve Fibers ◽  
Antral Mucosa ◽  
Nerve Supply ◽  
Vagus Nerves ◽  
Vagus Stimulation ◽  
Gastrin Secretion ◽  
Stimulation Of

By immunohistochemistry, nerve fibers containing gastrin-releasing polypeptide (GRP)-like immunoreactivity were identified close to the somatostatin (SS)-producing cells of the gastric antral mucosa. We, therefore, studied the possible role of GRP in the control of antral SS secretion by use of isolated perfused pig antrum with intact vagus nerve supply. Electrical stimulation of the vagus nerves at 4 Hz increased the antral release of GRP up to 10-fold and increased SS output 2- to 3-fold. Atropine at 10(-6) M had no effect on these responses. Intra-arterial GRP increased SS secretion significantly at 10(-10) M and eightfold at 10(-8) M, whereas gastrin secretion was stimulated significantly at 10(-11) M and maximally at 10(-10) M and inhibited at 10(-8) M. Preperfusion with a GRP antagonist ([D-Arg1,D-Pro2,D-Trp7,9,Leu11]substance P) or Fab fragments of antibodies against GRP abolished the effects of vagus stimulation on gastrin and somatostatin output. Gastrin in concentrations up to 10(-7) M was without effect on SS secretion. We conclude that electrical stimulation of the vagus nerves increases antral SS gastrin secretion and that GRP is a likely transmitter.

Synthesis of a Substance P Antagonist with a Somatostatin Scaffold:  Factors Affecting Agonism/Antagonism at GPCRs and the Role of Pseudosymmetry

2000 ◽  
Vol 43 (21) ◽  
pp. 3827-3831 ◽  
Author(s):  
Josephine Liu ◽  
Dennis J. Underwood ◽  
Margaret A. Cascieri ◽  
Susan P. Rohrer ◽  
Louis-David Cantin ◽  
...  
Keyword(s):  
Substance P ◽  
Factors Affecting ◽  
Substance P Antagonist

Role of Nitric Oxide towards Vasodilator Effects of Substance P and ATP in Human Forearm Vessels

1997 ◽  
Vol 92 (2) ◽  
pp. 123-131 ◽  
Author(s):  
Masanari Shiramoto ◽  
Tsutomu Imaizumi ◽  
Yoshitaka Hirooka ◽  
Toyonari Endo ◽  
Takashi Namba ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Substance P ◽  
Sodium Nitroprusside ◽  
Forearm Blood Flow ◽  
Dependent Manner ◽  
Human Forearm ◽  
Before And After ◽  
Dose Dependent

1. It has been shown in animals that substance P as well as acetylcholine releases endothelium-derived nitric oxide and evokes vasodilatation and that ATP-induced vasodilatation is partially mediated by nitric oxide. The aim of this study was to examine whether vasodilator effects of substance P and ATP are mediated by nitric oxide in humans. 2. In healthy volunteers (n = 35), we measured forearm blood flow by a strain-gauge plethysmograph while infusing graded doses of acetylcholine, substance P, ATP or sodium nitroprusside into the brachial artery before and after infusion of NG-monomethyl-l-arginine (4 or 8 μmol/min for 5 min). In addition, we measured forearm blood flow while infusing substance P before and during infusion of l-arginine (10 mg/min, simultaneously), or before and 1 h after oral administration of indomethacin (75 mg). 3. Acetylcholine, substance P, ATP or sodium nitroprusside increased forearm blood flow in a dose-dependent manner. NG-Monomethyl-l-arginine decreased basal forearm blood flow and inhibited acetylcholine-induced vasodilatation but did not affect substance P-, ATP-, or sodium nitroprusside-induced vasodilatation. Neither supplementation of l-arginine nor pretreatment with indomethacin affected substance P-induced vasodilatation. 4. Our results suggest that, in the human forearm vessels, substance P-induced vasodilatation may not be mediated by either nitric oxide or prostaglandins and that ATP-induced vasodilatation may also not be mediated by nitric oxide.

Role of NK1 tachykinin receptors in thermonociception: Effect of (±)-CP 96,345, a non-peptide substance P antagonist, on the hot plate test in mice

1991 ◽  
Vol 129 (2) ◽  
pp. 299-302 ◽  
Author(s):  
Alessandro Lecci ◽  
Sandro Giuliani ◽  
Riccardo Patacchini ◽  
Giovanni Viti ◽  
Carlo Alberto Maggi
Keyword(s):  
Substance P ◽  
Hot Plate ◽  
Hot Plate Test ◽  
Tachykinin Receptors ◽  
Plate Test ◽  
Substance P Antagonist

Role of Substance P in the Vascular Response of Nasal Mucosa in Nasal Allergy

1996 ◽  
Vol 105 (8) ◽  
pp. 648-653 ◽  
Author(s):  
Akiyoshi Konno ◽  
Toyoyuki Hanazawa ◽  
Tsutomu Numata ◽  
Hiroshi Nagata ◽  
Nobuhisa Terada ◽  
...  
Keyword(s):  
Blood Flow ◽  
Substance P ◽  
Sensory Stimulation ◽  
Nasal Allergy ◽  
Vascular Response ◽  
Nasal Challenge ◽  
C Fiber ◽  
Capacitance Vessels ◽  
Dose Dependent

The effects of topically administered substance P (SP) on nasal blood flow and nasal airway resistance (NAR) were evaluated in 11 subjects with perennial nasal allergy. The change in NAR induced by SP was compared with those induced by nasal challenge with histamine, leukotriene EM (LTD4), and antigen. In doses ⩾ 16 nmol, SP caused a significant increase of nasal blood flow within 5 minutes that lasted for less than 20 minutes. In doses ⩾16 nmol, SP caused a dose-dependent, short-lasting, significant increase in NAR. The magnitude of the increase in NAR was LTD4 > SP > histamine when compared on a molar basis. Our results may suggest that SP released from C fiber terminals is partially involved in an early nasal vascular response after antigen challenge by acting on adjacent vascular smooth muscle to cause a transient vasodilatation of both resistance and capacitance vessels only while sensory stimulation persists in subjects with nasal allergy.

Effects of the Neuropeptide, Substance P, on Lymphocyte Proliferation in Rheumatoid Arthritis

1995 ◽  
Vol 23 (6) ◽  
pp. 431-438 ◽  
Author(s):  
M Jovas ◽  
L A Pinto ◽  
J A Pereira da Silva ◽  
R M M Victorino
Keyword(s):  
Rheumatoid Arthritis ◽  
Substance P ◽  
Lymphocyte Proliferation ◽  
Mononuclear Cells ◽  
Thymidine Incorporation ◽  
Lymphocyte Activation ◽  
Dependent Manner ◽  
Peripheral Blood Mononuclear ◽  
Dose Dependent

There is evidence supporting the involvement of the neuropeptide, substance P, in the pathogenesis of rheumatoid arthritis. In view of the suggested role of T-cells in this disease, we have investigated the effects of substance P on mitogen-induced lymphocyte proliferation in rheumatoid arthritis patients. The peripheral blood mononuclear cells from 20 patients with rheumatoid arthritis and 25 controls were cultured in the presence or absence of substance P (10−-10 M to 10−-6 M) and stimulated with phytohaemagglutinin or concanavalin A. After 3 days of culture the proliferative responses were determined by measuring [3H]thymidine incorporation into the cells. Substance P enhanced, in a dose-dependent manner, the lymphocyte proliferative responses both in rheumatoid arthritis patients and in controls. Although there was a trend towards a greater enhancing effect in the rheumatoid arthritis patients, this was not statistically significant. Some individual patients with rheumatoid arthritis showed enhancements of lymphocyte proliferation with substance P that were clearly outside the range seen in healthy controls. The possibility that substance P has a role in the pathogenesis of rheumatoid arthritis through the up-regulation of lymphocyte activation should be considered in further studies of the immunomodulatory properties of substance P in arthritis.

Effect of vagus, gastric inhibitory polypeptide, and HCl on gastrin and somatostatin release from perfused pig antrum

1983 ◽  
Vol 244 (5) ◽  
pp. G515-G522 ◽  
Author(s):  
J. J. Holst ◽  
S. L. Jensen ◽  
S. Knuhtsen ◽  
O. V. Nielsen ◽  
J. F. Rehfeld
Keyword(s):  
Hydrochloric Acid ◽  
Portal Vein ◽  
Opposite Effect ◽  
Vagal Stimulation ◽  
Gastric Inhibitory Polypeptide ◽  
Artificial Medium ◽  
Gastrin Secretion ◽  
Vagal Innervation

The porcine antrum was isolated with the pancreas and perfused in vitro with an artificial medium supplemented with erythrocytes. The vagal innervation was preserved. Effluent was collected from the portal vein as well as from a vein directly draining the antrum. Electrical vagal stimulation increased gastrin output and inhibited somatostatin output. Intraluminal hydrochloric acid had the opposite effect. Gastric inhibitory polypeptide (GIP) in physiological concentrations (90 and 450 pmol/l) increased somatostatin output, inhibited gastrin output, and potentiated the effect of HCl on somatostatin release. Vagal stimulation, however, abolished the GIP effect on somatostatin output. Thus gastrin and somatostatin outputs were always inversely affected by the applied stimuli, suggestive of somatostatin-mediated control of gastrin secretion. GIP may exert its effects via local somatostatin release.

The role of the cholinergic systems in the central control of thermoregulation in rats

1979 ◽  
Vol 57 (11) ◽  
pp. 1205-1212 ◽  
Author(s):  
M. T. Lin ◽  
F. F. Chen ◽  
Y. F. Chern ◽  
T. C. Fung
Keyword(s):  
Heat Loss ◽  
Heat Production ◽  
Nerve Fibers ◽  
Cholinergic Receptors ◽  
Evaporative Heat Loss ◽  
Central Administration ◽  
Ambient Temperatures ◽  
Dose Dependent ◽  
Selective Blocker

Systemic and central administration of methacholine (a synthetic choline derivative) both produced dose-dependent decreases in rectal temperature in rats at all the ambient temperatures studied. Both at room temperature (22 °C) and in the cold (8 °C), the hypothermia in response to methacholine application was brought about by both a decrease in metabolic heat production and an increase in cutaneous circulation. In the heat (29 °C), the hypothermia was due solely to an increase in respiratory evaporative heat loss. Furthermore, the methacholine-induced hypothermia was antagonized by central pretreatment of atropine (a selective blocker of cholinergic receptors), but not by the central administration of either 6-hydroxy-dopamine (a relative depletor of catecholaminergic nerve fibers) or 5,6-dihydroxytryptamine (predominately a serotonin depletor). The data indicate that activation of the cholinergic receptors within brain with methacholine decreases heat production and (or) increases heat loss which leads to hypothermia in rats.

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