Mechanism of action of capsaicin on submucosal arterioles in the guinea pig ileum

1993 ◽  
Vol 265 (1) ◽  
pp. G51-G55 ◽  
Author(s):  
S. Vanner
Keyword(s):  
Guinea Pig ◽  
Mechanism Of Action ◽  
Sensory Nerves ◽  
Human Calcitonin ◽  
Prostaglandin F2 Alpha ◽  
Afferent Fibers ◽  
Calcitonin Gene ◽  
Muscarinic Receptor Antagonists ◽  
Repeated Applications

Vasomotor neurons in the enteric nervous system release acetylcholine to dilate submucosal arterioles, but it is not known whether sensory nerves that project to these vessels also can provide a vasodilator innervation. This possibility was examined by determining the mechanism of action of capsaicin on guinea pig ileal submucosal arterioles in vitro. Capsaicin dilated all vessels that had been preconstricted with prostaglandin F2 alpha; mean effective concentration was 11 nM, and maximal dilation occurred at 60-200 nM. The vasodilation showed marked desensitization upon repeated applications of capsaicin. Tetrodotoxin blocked the capsaicin-induced vasodilation but not the desensitization observed upon repeated application. Muscarinic receptor antagonists did not affect the actions of capsaicin. Capsaicin did not dilate arterioles whose extrinsic sensory afferent fibers had been surgically removed. Substance P and human calcitonin gene-related peptide II dilated arterioles; these dilations were not inhibited after desensitization of the capsaicin-induced vasodilation. Thus capsaicin dilates submucosal arterioles by selectively activating extrinsic afferent fibers that release vasodilator transmitter substances onto these vessels.

Release of Calcitonin Gene-Related Peptide (CGRP) from Guinea Pig Dura Mater in vitro is Inhibited by Sumatriptan But Unaffected by Nitric Oxide

Cephalalgia ◽  
2000 ◽  
Vol 20 (9) ◽  
pp. 838-844 ◽  
Author(s):  
CT Eltorp ◽  
I Jansen-Olesen ◽  
AJ Hansen
Keyword(s):  
Nitric Oxide ◽  
Guinea Pig ◽  
Dura Mater ◽  
Sensory Nerves ◽  
High Potassium ◽  
Cgrp Release ◽  
Calcitonin Gene ◽  
High Potassium Concentration

Migraine attacks can be provoked by administration of nitroglycerin, suggesting a role for nitric oxide (NO). The fact that release of the neuropeptide CGRP from trigeminal sensory nerves occurs during the pain phase of migraine and that NO can augment transmitter release prompted us to study CGRP release from the in situ dura mater in guinea pig skulls. Release of CGRP by capsaicin or by high potassium concentration was concentration-dependent and counteracted in calcium-free medium. The anti-migraine compound, sumatriptan, inhibited CGRP release via the 5-HT1-receptor. The NO donors, nitroglycerin, sodium nitroprusside and S-nitroso-N-acetylpenicillamine did not influence CGRP release, alone or together with the stimulants. We concluded that the skull preparation is well suited for scrutinizing CGRP release from dura mater. The fact that sumatriptan inhibits CGRP release as in migraine patients suggests a use for the present preparation in headache research.

Calcitonin gene related peptide relaxes cholecystokinin-induced contraction in guinea pig gallbladder strips in vitro

1992 ◽  
Vol 70 (12) ◽  
pp. 1571-1575 ◽  
Author(s):  
L. W. Kline ◽  
P. K. T. Pang
Keyword(s):  
Smooth Muscle ◽  
Guinea Pig ◽  
Calcitonin Gene Related Peptide ◽  
Intestinal Smooth Muscle ◽  
Human Calcitonin ◽  
Peptide Receptor ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Dose Dependent

Calcitonin gene related peptide has been shown to relax vascular and intestinal smooth muscle. This study examines the effects of calcitonin gene related peptide on cholecystokinin-induced contraction of guinea pig gallbladder strips in vitro. Calcitonin gene related peptide was found to cause a dose-dependent relaxation of cholecystokinin-induced tension, which was blocked by the calcitonin gene related peptide receptor antagonist human calcitonin gene related peptide8–37. Previous studies demonstrated that calcitonin gene related peptide acted directly on guinea pig gallbladder smooth muscle to inhibit acetylcholine- or KCl-induced contraction. The present results further confirm that calcitonin gene related peptide acts directly on the smooth muscle. In addition, the use of L-NG-nitroarginine methyl ester, glibenclamide, and other agents strongly suggests that calcitonin gene related peptide also acts by way of the nonadrenergic noncholinergic nervous system, to induce the relaxation of cholecystokinin-induced contraction observed in the guinea pig gallbladder strips.Key words: calcitonin gene related peptide, gallbladder, cholecystokinin.

Beta 2-adrenoceptor agonists inhibit NANC neural bronchoconstrictor responses in vitro

1993 ◽  
Vol 74 (3) ◽  
pp. 1195-1199 ◽  
Author(s):  
G. M. Verleden ◽  
M. G. Belvisi ◽  
K. F. Rabe ◽  
M. Miura ◽  
P. J. Barnes
Keyword(s):  
Substance P ◽  
Guinea Pig ◽  
Electrical Field Stimulation ◽  
Sensory Nerves ◽  
Inhibitory Effects ◽  
Exogenous Substance ◽  
Dependent Inhibition ◽  
Adrenoceptor Agonists ◽  
Beta 2

Nonadrenergic noncholinergic (NANC) contractile responses in guinea pig bronchi are due to the release of tachykinins from airway sensory nerves. The purpose of this study was to determine whether beta 2-receptor agonists modulate NANC contractions in guinea pig bronchi in vitro. Bronchial rings were suspended in organ baths for isometric measurement of tension, and comparable contractions were induced by electrical field stimulation (EFS; 40 V, 0.5 ms, 8 Hz for 20 s) or by exogenous substance P (3 microM). Aformoterol and salbutamol produced concentration-dependent inhibition of the NANC contraction, with aformoterol being ninefold more potent than salbutamol; approximate 50% inhibitory concentrations for aformoterol and salbutamol were 1.03 nM (n = 6) and 9.3 nM (n = 6), respectively. Aformoterol also inhibited the contraction induced by exogenous substance P but to a far lesser extent than its inhibition of EFS-induced responses. The inhibitory effects of formoterol (10 nM) on responses to EFS at 8 Hz were significantly prevented by propranolol (1 microM) and ICI 118551 (a beta 2-antagonist, 0.1 microM) but not by atenolol (a beta 1-antagonist, 1 microM) or phentolamine (10 microM). These experiments demonstrate that beta 2-agonists may modulate the release of tachykinins from airway sensory nerves by prejunctional receptors.

Capsaicin-sensitive afferent nerves activate submucosal secretomotor neurons in guinea pig ileum

1995 ◽  
Vol 269 (2) ◽  
pp. G203-G209 ◽  
Author(s):  
S. Vanner ◽  
W. K. MacNaughton
Keyword(s):  
Guinea Pig ◽  
Ion Transport ◽  
Short Circuit ◽  
Ussing Chamber ◽  
Sensory Nerve ◽  
Nerve Fibers ◽  
Sensory Nerves ◽  
Guinea Pig Ileum ◽  
Secretomotor Neurons

This study examined whether capsaicin-sensitive sensory nerves regulate intestinal ion transport using both Ussing chamber and intracellular recording techniques in in vitro submucosal preparations from the guinea pig ileum. In Ussing chamber studies, serosal application of capsaicin (20 nM-20 microM) evoked a biphasic dose-dependent increase in short-circuit current (Isc) (maximal effective concentration 200 nM and 2 microM, respectively). In chloride-free buffer, capsaicin responses were significantly reduced. Capsaicin evoked little or no response when extrinsic sensory nerve fibers had been surgically removed and tetrodotoxin and low-calcium and high-magnesium solutions blocked responses to capsaicin. In epithelial preparations devoid of submucosal neurons, capsaicin had virtually no effect, suggesting that responses evoked by capsaicin-sensitive nerves result from activation of submucosal secretomotor neurons. Intracellular recordings from single submucosal neurons demonstrated that superfusion with capsaicin (2 microM) depolarized neurons with an associated decreased conductance. Depolarizations were completely desensitized when capsaicin was reapplied, but synaptic inputs were unaffected. This study suggests that capsaicin-sensitive nerves can regulate ion transport in the gastrointestinal tract by release of neurotransmitter(s) that activate submucosal secretomotor neurons.

scholarly journals The role of the sensory peptide calcitonin-gene-related peptide(s) in skeletal muscle carbohydrate metabolism: effects of capsaicin and resiniferatoxin

1995 ◽  
Vol 307 (3) ◽  
pp. 707-712 ◽  
Author(s):  
B Leighton ◽  
E A Foot
Keyword(s):  
Skeletal Muscle ◽  
Soleus Muscle ◽  
Glycogen Synthesis ◽  
Calcitonin Gene Related Peptide ◽  
Sensory Nerves ◽  
Muscle Fibres ◽  
Related Peptide ◽  
Calcitonin Gene

1. The content of calcitonin-gene-related-peptide-like immunoreactivity (CGRP-LI) in various rat muscles was measured. Starvation for 24 h did not affect the content of CGRP-LI in these muscles, except for a decreased level in the starved-rat diaphragm. Higher contents of CGRP-LI were observed in well-vascularized muscles. 2. Capsaicin (at 1, 10 and 100 microM) inhibited insulin-stimulated rates of glycogen synthesis in isolated stripped incubated soleus muscle preparations by a mechanism independent of catecholamine release, since the effects of capsaicin were not altered by the beta-adrenoreceptor antagonist DL-propranolol. 3. Resiniferatoxin (10 nM), which is a potent capsaicin agonist, also significantly inhibited the insulin-stimulated rate of glycogen synthesis. Furthermore, the concentration of resiniferatoxin required to inhibit glycogen synthesis was 100 times less than the concentration of capsaicin needed for the same effect. 4. Capsaicin (10 microM) decreased the content of CGRP-LI in isolated stripped incubated soleus muscle preparations by about 40%. 5. Neonatal treatment of rats with capsaicin, which causes de-afferentation of some sensory nerves such, we hypothesize, that CGRP can no longer be released to counteract the effects of insulin in vivo, caused increased rates of glycogen synthesis and increased glycogen content in stripped soleus muscle preparations in vitro when muscles were isolated from the adult rats. 6. These findings support the hypothesis that capsaicin and resiniferatoxin elicit an excitatory response on sensory nerves in skeletal muscle in vitro to cause the efferent release of CGRP. Consequently, CGRP is delivered to skeletal muscle fibres to inhibit insulin-stimulated glycogen synthesis. The role of CGRP in recovery of blood glucose levels during hypoglycaemia is discussed.

scholarly journals Inhibition of pulmonary prostaglandin metabolism by exposure of animals to oxygen or nitrogen dioxide

1979 ◽  
Vol 184 (1) ◽  
pp. 51-57 ◽  
Author(s):  
A Chaudhari ◽  
K Sivarajah ◽  
R Warnock ◽  
T E Eling ◽  
M W Anderson
Keyword(s):  
Guinea Pig ◽  
Competitive Inhibition ◽  
Systemic Circulation ◽  
Prostaglandin Metabolism ◽  
Prostaglandin F2 Alpha ◽  
Prostaglandin Dehydrogenase ◽  
Perfused Lung ◽  
Glucose 6 Phosphate Dehydrogenase ◽  
Lung And Kidney

The effects of exposure of animals to 100% O2 and NO2 on the rate of prostaglandin metabolism by lung and kidney were studied in vitro. Exposure of guinea pigs to 100% O2 for 48 h inhibited the metabolism of prostaglandin F2 alpha by both NAD+- and NADP+-dependent prostaglandin dehydrogenase in lung, but had no effect on the metabolism in kidney. Succinate dehydrogenase, but not glucose 6-phosphate dehydrogenase, in guinea-pig lung was inhibited by exposure to 100% O2. Exposure to 46 p.p.m. but not 16 or 29 p.p.m. NO2 for 6 h inhibited guinea-pig lung prostaglandin dehydrogenase in vitro. The inhibition of pulmonary prostaglandin dehydrogenase by exposure to 100% O2 or to 49 p.p.m. NO2 was dependent on the duration of exposure, but returned to control values within 7 days after cessation of the exposure. The pulmonary transport system responsible for removing circulating prostaglandins from the blood was not affected by exposure to 100% O2 as measured by using the isolated perfused lung. Kinetic analysis of the inhibition of pulmonary prostaglandin dehydrogenase activity in guinea pig exposed to 100% O2 showed non-competitive inhibition with respect to both prostaglandin F2 alpha and NAD+, which suggests destruction or inactivation of the enzyme. Pulmonary prostaglandin dehydrogenase appears to be inhibited by exposure to oxidant gases, which may lead to elevated prostaglandin concentrations in the lungs or in the systemic circulation.

Calcitonin gene-related peptide as potential neurotransmitter in guinea pig right atrium

1986 ◽  
Vol 250 (4) ◽  
pp. H693-H698 ◽  
Author(s):  
A. Saito ◽  
S. Kimura ◽  
K. Goto
Keyword(s):  
Guinea Pig ◽  
Right Atrium ◽  
Sinus Node ◽  
Calcitonin Gene Related Peptide ◽  
Dependent Manner ◽  
Chronotropic Response ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
The Right

The potential neurotransmitter role of calcitonin gene-related peptide (CGRP) in cardioacceleratory nonadrenergic noncholinergic (NANC) nerves was examined in the guinea pig right atrium in vitro. In the presence of atropine, a muscarinic antagonist, and atenolol, a beta-adrenoceptor antagonist, transmural nerve stimulation (TNS) of the isolated right atrium caused a positive chronotropic response, which is slow in both onset and decay. This TNS-induced slow response was assumed to be mediated by NANC nerves in the right atrium since tetrodotoxin inhibited the response. Dense distribution of CGRP-like immunoreactive (CGRP-I) nerves was demonstrated in the sinus node. Exogenously applied CGRP exerted a positive chronotropic effect on the isolated right atrium in a dose-dependent manner. Both CGRP-I nerves and NANC response induced by TNS were not affected by surgical sympathectomy and reserpine pretreatment but were abolished by the pretreatment of animals with capsaicin. The results suggest that CGRP is the neurotransmitter of cardioacceleratory NANC nerves in the right atrium of the guinea pig.

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