DrugBank:EXPT02427 - FACTA Search

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Query: DrugBank:EXPT02427 (Atropine)
3,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the relaxant effect of electric field stimulation (EFS) on rabbit cavernous smooth muscle strips in vitro precontracted by phenylephrine. Effects of EFS were monitored alone, and following muscarinic receptor blockade, and inhibition of nitric oxide (NO) formation by L-N-monomethylarginine (L-NMMA) or by L-N-nitroarginine (L-NOARG). Atropine only slightly reduced the relaxant effect of EFS to 89.0 +/- 6.1 percent. Additional application of L-NMMA further reduced the relaxant effect to 37.3 +/- 15.3 percent. Substitution of L-NOARG for L-NMMA led to a more pronounced inhibition of relaxant effects to 16.2 +/- 8.7 percent. The results indicate that neurogenically induced relaxation of rabbit cavernous smooth muscle is mediated mainly by NO formation and argue against a substantial role of relaxing peptidergic neurotransmitters, such as vasoactive intestinal polypeptide and calcitonin-gene-related peptide, in penile erection.
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PMID:Nitric oxide mediates neurogenic relaxation induced in rabbit cavernous smooth muscle by electric field stimulation. 144 Oct 51

(1) Circularly-oriented muscle strips from the human ileum responded to electrical field stimulation (1-50 Hz) with frequency-related primary relaxation at low frequency and primary contractions at high frequencies of stimulation. Both responses were abolished or markedly reduced by tetrodotoxin (1 microM). (2) Atropine (3 microM) or omega conotoxin (0.1 microM) reduced but dit not abolish contraction to electrical field stimulation and enhanced the relaxation. Omega conotoxin (0.1 microM) did not affect carbachol-induced contraction nor isoprenaline-induced relaxation. (3) Neurokinin A and substance P (1 nM-1 microM) produced a concentration-dependent contraction. The NK-1 receptor selective agonist, [Pro9]SP sulfone and the NK-2 receptor selective agonist [beta Ala8]NKA(4-10) produced a contraction superimposable to that of substance P and neurokinin A, respectively. On the other hand, [MePhe7]-neurokinin B, an NK-3 receptor selective agonist was ineffective up to 1 microM. The response to substance P or neurokinin A was unaffected by atropine (3 microM). (4) Galanin, up to 0.1 microM, produced a weak and inconsistent contraction. (5) Vasoactive intestinal polypeptide (10 nM-1 microM) produced a concentration-dependent relaxation while human alpha calcitonin gene-related peptide exerted a weak and inconsistent relaxant effect. (6) These findings indicate that both cholinergic excitatory and non-cholinergic inhibitory nerves affect the motility of the circular muscle of the human small intestine. Transmitter release from excitatory nerves seems largely mediated by activation of omega conotoxin-sensitive (N-type) calcium channels. Tachykinins exert a potent contractile effect, independently of cholinergic nerves, via NK-1 and NK-2 receptors.
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PMID:Human isolated ileum: motor responses of the circular muscle to electrical field stimulation and exogenous neuropeptides. 169 76

The innervation of the heart of the snake Elaphe obsoleta was examined with peptide immunohistochemistry, glyoxylic acid-induced catecholamine fluorescence, and in vitro physiological preparations. Snakes were anesthetized with Nembutal. Many somatostatin (SOM)-like immunoreactive (LI) axons were observed in the sinus venosus, atria, and ventricle. Cell bodies with SOM-LI were found in the intracardiac nerve trunks of the sinus venosus, the interatrial septum, and the atrioventricular region. The SOM-LI axons and cell bodies were not affected by 6-hydroxy-dopamine and capsaicin. They are probably intrinsic parasympathetic neurons. Adrenergic, neuropeptide Y-LI, substance P-LI, and calcitonin gene-related peptide-LI axons were found in the sinus venosus, atria, and ventricle. In spontaneously beating sinoatrial or electrically driven atrial preparations, applied SOM (6 x 10(-9) M and 6 x 10(-8) M) decreased the force of atrial contraction and/or the rate of beating. The effects of SOM were tachyphylactic. SOM had no effect on the force of contraction of the driven ventricle. Stimulation of the left and right vagus nerves elicited negative chronotropic and inotropic responses followed by poststimulus positive inotropic and chronotropic responses. Atropine abolished the inhibition, and bretylium abolished the excitation. After cholinergic and adrenergic blockade, high-frequency vagal nerve stimulation had no effect on heart rate and the force of contraction. Thus, although there is an extensive distribution of intrinsic SOM-LI neurons in the heart and although applied SOM is a potent inhibitor of rate and force, SOM in the vagal neurons does not appear to act as a direct inhibitory transmitter to the cardiac muscle or pacemaker cells.
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PMID:Somatostatin and innervation of the heart of the snake Elaphe obsoleta. 197 Apr 54

This study examined the effects of electrically stimulating submucosal neurons in the guinea pig isolated distal colonic mucosa and determined the effects of several peptides that are present in these neurons. Electrical field stimulation of muscle-stripped segments of guinea pig distal colonic mucosa, set up in Ussing flux chambers, evoked an increase in short-circuit current (Isc), of 371 +/- 31 MicroA.cm-2. The response to electrical stimulation was abolished by tetrodotoxin and significantly reduced by serosal furosemide. Atropine reduced, but did not abolish, the neurally evoked response. Addition of neuropeptide Y and galanin to the serosal bath had no effect on baseline Isc, but both evoked a concentration-dependent decrease in the neurally evoked secretory response. Vasoactive intestinal polypeptide evoked a concentration-dependent increase in basal (unstimulated) Isc that was reduced by furosemide and unaltered by tetrodotoxin. Neuropeptide Y, but not galanin, significantly reduced the secretory responses to vasoactive intestinal polypeptide and bethanechol. Somatostatin 201-995 and human calcitonin gene-related peptide had no effect on basal Isc nor did either alter the neurally evoked response. These results suggest that acetylcholine and non-cholinergic neurotransmitter(s) stimulate chloride secretion in the guinea pig distal colonic mucosa. This neurosecretory response may be modulated by neuropeptide Y and galanin that are found within submucosal neurons.
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PMID:Neuropeptide modification of chloride secretion in guinea pig distal colon. 244 52

The role of rat calcitonin gene-related peptide (CGRP), a recently characterized vasoactive neuropeptide, in cardiovascular regulation was studied in the conscious rat. Mean arterial pressure (MAP), heart rate, cardiac output (thermodilution technique) and regional blood flow (directional pulsed Doppler velocimetry) were monitored after i.v. or i.c.v. administration of CGRP. Systemic administration of CGRP (0.1-10 nmol/kg i.v.) decreased MAP and increased heart rate in a dose-related manner. Cardiac output increased (+95 +/- 16 ml/min/kg, P less than .01) after the 1-nmol/kg dose. At the lower or higher doses, CGRP produced no consistent changes in cardiac output. Total peripheral resistance was decreased significantly at the doses of 1 and 10 nmol/kg of CGRP. The CGRP i.v. doses of 1 and 10 nmol/kg increased mesenteric and hindquarter blood flow to a maximum of +23 +/- 7 and +30 +/- 6%, respectively (P less than .01). An increase in renal blood flow (+19 +/- 6%, P less than .05) and a decrease in renal resistance (-15 +/- 4%, P less than .05) were produced by the 0.1-nmol/kg dose of CGRP which had no effect on MAP; higher doses of CGRP tended to decrease renal blood flow. The resistance in all vascular beds was decreased by the CGRP doses of 1 and 10 nmol/kg. The maximum decreases in mesenteric, renal and hindquarter vascular resistance after the 10-nmol/kg dose were -53 +/- 3, -42 +/- 5 and -48 +/- 4%, respectively (P less than .01). The hypotensive and vasodilator responses to CGRP i.v. were significantly magnified, and the tachycardia produced by CGRP was attenuated in the sinoaortic denervated rats. Atropine (muscarinic blockers), propranolol (beta adrenoceptor blocker), cimetidine and pyrilamine (histamine H1 and H2 blockers), indomethacin (prostaglandin synthesis inhibitor), BN52021 (platelet activating factor antagonist) or a substance P antagonist had no effect on the cardiovascular responses elicited by systemic CGRP. CGRP, i.c.v. (0.1-10 nmol/kg), induced a modest tachycardia in both intact and sinoaortic denervated rats, but was devoid of any other cardiovascular effects. The results indicate that CGRP is a potent vasodilator of mesenteric, renal and hindquarter skeletal muscle blood vessels in the conscious rat. The hypotensive and vasodilator actions of circulating CGRP are likely to be mediated by direct peripheral interaction with CGRP receptors on vascular smooth muscle, whereas its tachycardic effect seems to involve reflex activation of the sympathetic nervous system.
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PMID:Cardiovascular effects of rat calcitonin gene-related peptide in the conscious rat. 245 71

1. 'Atropine-resistant' secretion of saliva in response to parasympathetic stimulation may reflect antidromic activation of sensory nerve fibres. In this investigation, the effect of pretreatment in the rat with capsaicin (total dose of 125 mg kg-1, s.c.), was determined. 2. In the parotid glands substance P (SP)/calcitonin gene-related peptide (CGRP)-containing nerve fibres around ducts and blood vessels disappeared after capsaicin, while periacinar SP-containing fibres (devoid of CGRP) and CGRP-containing fibres (devoid of SP) remained. Vasoactive intestinal peptide (VIP)-containing nerve fibres seemed to be unaffected. The parotid content of SP and CGRP was reduced by 11 and 36% respectively, while that of VIP remained unchanged. 3. The weights of the parotid glands and their sensitivity to the secretagogues methacholine and SP, injected intravenously, were unchanged as was the response to stimulation of the auriculo-temporal nerve in the presence and absence of atropine. 4. In contrast to capsaicin pretreatment, parasympathetic denervation of the parotid gland reduced the weight of the gland and produced an increase in the response to methacholine and SP. 5. For comparison, the effectiveness of the capsaicin treatment on neuropeptide content was determined in the urinary bladder. The bladder of capsaicin-pretreated rats increased in weight (21%) and in VIP content (31%), while the content of SP and CGRP was reduced by 86 and 94%, respectively. SP- and CGRP-containing nerve fibres were virtually eliminated, while VIP-containing nerve fibres seemed unaffected. 6. In conclusion, antidromic activation of primary afferent (capsaicin-sensitive) C-fibres does not contribute significantly to the 'atropine-resistant' secretory response of the parotid gland to stimulation of the parasympathetic nerve.
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PMID:Effects of capsaicin pretreatment on neuropeptides and salivary secretion of rat parotid glands. 247 1

The central nervous system effects of thyrotropin-releasing hormone (TRH) and calcitonin gene-related peptide (CGRP) on exocrine pancreatic secretion were studied in freely moving rats. TRH (0.05-0.5 nmol) significantly stimulated, whereas CGRP (0.1-1.0 nmol) significantly inhibited, volume, protein, and bicarbonate secretion. Pretreatment of the animals with the ganglionic blocking agent chlorisondamine abolished the pancreatic responses produced by both peptides. In contrast, vagotomy abolished the stimulatory effect of TRH, whereas noradrenergic blockade with bretylium or phentolamine abolished the inhibitory effect of CGRP. Atropine significantly attenuated, but the vasoactive intestinal peptide (VIP) antagonist [D-p-Cl-Phe6, Leu17]VIP completely abolished the stimulatory effect of TRH. Pancreatic secretory responses stimulated by cerebral TRH or by peripheral VIP were inhibited dose dependently by peripheral [D-p-Cl-Phe6,Leu17]VIP. Inhibition of pancreatic secretion induced by cerebral CGRP or by peripheral norepinephrine was prevented by intravenous phentolamine. These results indicate 1) cerebral TRH stimulates and cerebral CGRP inhibits exocrine pancreatic secretion in freely moving rats; 2) the effects of TRH are mediated by vagal efferents, and the primary peripheral transmitter appears to be VIP acting on VIP receptors, whereas muscarinic efferents are less important; and 3) the effects of CGRP are mediated by sympathetic noradrenergic efferents via alpha-adrenergic receptors.
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PMID:Regulation of exocrine pancreatic secretion by cerebral TRH and CGRP: role of VIP, muscarinic, and adrenergic pathways. 844 6

The effects of human alpha-calcitonin gene-related peptide (alpha-CGRP), beta-CGRP, and vasoactive intestinal polypeptide (VIP) on left gastric (LGA) and superior mesenteric arterial (SMA) blood flow, heart rate and systemic arterial blood pressure were investigated in 6 conscious beagle dogs. Both intravenous injections of alpha-CGRP and beta-CGRP (5-200 pmol/kg) and infusion of alpha-CGRP (25-100 pmol/kg per h) induced a dose-related increase in SMA flow and a dose-related decrease in its resistance. At lower doses, alpha-CGRP was more potent than beta-CGRP, but their maximal responses were the same. alpha-CGRP and beta-CGRP had little effect on LGA flow. However, alpha-CGRP at 200 pmol/kg, but not beta-CGRP, stimulated gastroduodenal contractions that were associated with a phasic increase of LGA flow. Atropine inhibited gastric, but not duodenal, motor and circulatory responses to alpha-CGRP. Tachycardia and hypotension induced by beta-CGRP were significantly less than those by alpha-CGRP. VIP, on the other hand, increased mainly LGA flow. These results suggest that blood vessels of the small intestine of dogs are more sensitive to CGRP than those of the stomach, while the sensitivity to VIP is reversed.
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PMID:Calcitonin gene-related peptide is a potent intestinal, but not gastric, vasodilator in conscious dogs. 889 44

Pain relief mechanisms of needling to the pain-producing muscle, application of a static magnetic field or external qigong, and needling to the acupuncture point were investigated in an experimentally designed pain producing muscle of animals. Single isometric twitch height in situ was reduced gradually by 10 Hz tetanic stimulation for one hour of the gastrocnemius muscle of guinea pigs. This reduction of twitch height was recovered by injection of 0.3-1 ml saline to the artery of this muscle, or of injection of a vasodilator, isoproterenol dissolved in 0.1 ml saline. Hence, reduction of twitch height could be induced by reduction of circulation in the muscle and recovery of it could be induced be recovery of circulation. Since it is easily considered that a pain substance might be accumulated in a muscle under reduced circulation, and such an accumulated substance might be eliminated by recovery of circulation, the reduction of twitch height after tetanic stimulation could be estimated as the pain-producing muscle and recovery of twitch, as the pain relieving muscle. 1) Needling to the pain muscle, 2) application of a static magnetic field or external qigong to the muscle, and 3) needling to the acupuncture point recovered the reduced twitch height due to tetanic stimulation. Atropine abolished this effect induced by the above 1, 2 and 3 procedures. Hence, the cholinergic vasodilator nerve might be involved in the induction of this effect. A sciatic nerve cut did not influence the effect of 1), but abolished the effect of 3). Denervation and capsaicin abolished the effect of 1). Substance P and a calcitonin gene- related peptide (CGRP) recovered the reduced twitch height, and atropine blocked the effect of CGRP, but did not block that of substance P. The effect of 2) was equivalent to that of anticholinesterase. A rostral lesion of the contralateral anterior hypothalamus did not abolish the effect of 3, but a caudal lesion of this region did. Electrical stimulation of this region produced an effect similar to that of 3). From these results, it was concluded that muscle pain relief by these procedures might be induced by recovery of circulation due to the enhanced release of acetylcholine as a result of activation of the cholinergic vasodilator nerve endings innervated to the muscle artery. However, manners of activation of the cholinergic nerve was different in effects of 1), 2) and 3). 1) might be induced by axon reflex of the CGRP nerve, 2) might be induced by inhibition of cholinesterase and 3) might be induced by a somato-autonomic reflex. The reflex center of this might be in the anterior hypothalamus.
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PMID:Comparisons of pain relief mechanisms between needling to the muscle, static magnetic field, external qigong and needling to the acupuncture point. 891 86

This study was designed to investigate the effect of porcine calcitonin gene-related peptide (CGRP) on the motility of the porcine biliary tract in vivo. We measured the pressure in the gallbladder and sphincter of Oddi and, in separate experiments, the biliary flow into the duodenum during local intraarterial infusions of CGRP. To determine if the observed effect could be caused by release of cholecystokinin (CCK), we measured the CCK release. The basal pressure in the sphincter of Oddi increased dose-dependently from 5.9 +/- 0.5 mmHg to 11.5 +/- 2.1 mmHg and the motility index of phasic contractions (amplitude x frequency) from 47 +/- 8 to 347 +/- 64 mmHg s-1, at an infusion rate of 32.6 pmol kg-1 min-1. No effect was observed on the gallbladder pressure. CGRP at 6.5 pmol kg-1 min-1 significantly reduced the biliary flow into the duodenum to 47.7 +/- 6% of the basal level. Atropine, injected intravenously, completely abolished the contractile effect of CGRP. CGRP had no effect on the release of CCK. We conclude that CGRP increases biliary motility and hereby reduces bile flow, an effect which involves cholinergic but not cholecystokininergic mechanisms.
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PMID:Calcitonin gene-related peptide (CGRP), a potent regulator of biliary flow. 943 Jul 89

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