Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:EXPT02427 (Atropine)
 3,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Secretagogues of pancreatic enzyme secretion, the hormones pancreozymin, carbamylcholine, gastrin I, the octapeptide of pancreozymin, and caerulein as well as the Ca++ -ionophore A 23187 stimulate 45Ca efflux from isolated pancreatic cells. The non-secretagogic hormones adrenaline, isoproterenol, secretion, as well as dibutyryl cyclic adenosine 3',5'-monophosphate and dibutyryl cyclic guanosine 3',5'-monophosphate have no effect on 45Ca efflux. Atropine blocks the stimulatory effect of carbamylcholine on 45Ca efflux complately, but not that of pancreozymin. A graphical analysis of the Ca++ efflux curves reveals at least three phases: a first phase, probably derived from Ca++ bound to the plasma membrane; a second phase, possibly representing Ca++ efflux from cytosol of the cells; and a third phase, probably from mitochondria or other cellular particles. The Ca++ efflux of all phases is stimulated by pancreozymin and carbamylcholine. Ca++ efflux is not significantly effected by the presence or absence of Ca++ in the incubation medium. Metabolic inhibitors of ATP production. Antimycin A and dinitrophenol, which inhibit Ca++ uptake into mitochondria, stimulate Ca++ efflux from the isolated cells remarkably, but inhibit the slow phase of Ca++ influx, indicating the role of mitochondria as an intracellular Ca++ compartment. Measurements of the 45Ca++ influx at different Ca++ concentrations in the medium reveal saturation type kinetics, which are compatible with a carrier or channel model. The hormones mentioned above stimulate the rate of Ca++ translocation. The data suggest that secretagogues of pancreatic enzyme secretion act by increasing the rate of Ca++ transport most likely at the level of the cell membrane and that Ca++ exchange diffusion does not contribute to the 45Ca++ fluxes.
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PMID:Ca++ fluxes in isolated cells of rat pancreas. effect of secretagogues and different Ca++ concentrations. 78 85

The effects of electrical field stimulation (EFS) of rabbit middle cerebral arteries were examined using wire-mounted arterial segments. EFS of segments maintained at rest tension caused a tetrodotoxin-sensitive sympathetic contraction. In agonist-contracted segments maintained at approximately 60% of tissue maximum force, EFS caused a relaxation in two thirds of the preparations. Maximum response (mean +/- SEM) was 33 +/- 3.5% of maximal relaxation. The EFS relaxation was tetrodotoxin-sensitive but was not blocked by either chronic surgical sympathectomy or exposure to guanethidine (5 microM). Electron microscopy of chromaffin-fixed arterial sections showed the presence of chromaffin-positive large and small vesicles. Within the same sheath of Schwann were also a smaller number of nerve profiles containing many small clear vesicles. Removal of the vascular endothelium or treatment with atropine (10 nM) eliminated the EFS relaxation in approximately 50% of the segments and reduced the response in another 35-40%; in the remainder, relaxation was unaffected. Combined data for endothelium removal and atropine treatment showed that each caused a significant (p less than 0.01) reduction in the EFS relaxation. Atropine also significantly reduced EFS relaxation in guanethidine-treated segments. There was no reduction in EFS relaxation after procedures that antagonized ATP- or substance P-mediated relaxations. These results indicate that EFS of precontracted rabbit middle cerebral artery causes a neurogenic nonadrenergic relaxation. The neuroeffector mechanism mediating this response has a predominantly cholinergic endothelium-dependent component as well as a noncholinergic endothelium-independent component.
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PMID:Electrical field stimulation-mediated relaxation of rabbit middle cerebral artery. Evidence of a cholinergic endothelium-dependent component. 134 15

1. Purine compounds were examined for pharmacological activity in the rectum and oesophagus of the garden snail Helix aspersa. 2. In the rectum, adenosine, AMP, ADP and ATP (above 10 microM) and acetylcholine (above 1 nM) consistently caused concentration-dependent contractions. The slope of the dose-response curve for ADP in the rectum was significantly steeper than for the other purine compounds. The contractile responses to the nucleotides and acetylcholine, but not adenosine, were selectively potentiated by physostigmine (1 microM). Atropine (1 microM) and tubocurarine (30 microM) failed to block the responses to the purines or acetylcholine. 3. In the oesophagus, adenosine, AMP, ADP and ATP (above 10 microM) and acetylcholine (above 1 nM) caused concentration-dependent contractions that were antagonised by atropine (1 microM). Tubocurarine (30 microM) failed to block the responses to the purine compounds or acetylcholine. Physostigmine (1 microM) potentiated the responses to ADP and acetylcholine but not ATP, AMP or adenosine. 4. In both the rectum and the oesophagus, the synthetic analogues of purine compounds including 2-chloroadenosine, alpha,beta-methylene ATP and 2-methylthio ATP were inactive up to a concentration of 100 microM. 5. Electrical field stimulation of the rectum and oesophagus produced consistent contractions which were unaffected by atropine (1 microM), tubocurarine (30 microM) or physostigmine (1 microM). These responses were not modulated by any of the purine compounds or their stable analogues. 6. The responses obtained appear novel even within known invertebrate purinergic systems, suggesting a differentiation of purinoceptor subtypes in this species.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Responses of the rectum and oesophagus of the snail Helix aspersa to purine nucleotides and nucleosides. 136 1

The response of the rabbit urinary bladder to field stimulation (80 volts, 2-32 Hz, 1 msec duration) is biphasic, consisting of an initial phasic contraction mediated by cholinergic and purinergic neurotransmitters, followed by a prolonged tonic contraction which is solely cholinergic. Obstructive hypertrophy of the bladder induces a variety of contractile alterations including a significantly greater reduction in the tonic component of the contractile response as compared to the phasic component. This results in a severe dysfunction in the ability of the bladder to empty. One possibility is that the inability of the bladder to maintain tension and empty efficiently may be related to a degeneration of nerves innervating the bladder smooth muscle. In addition to the well documented neuropathy, the bladder undergoes hypertrophy +/- hyperplasia of both smooth muscle and interstitial cellular elements, alterations in the metabolism of substrates, alterations in the synthesis of structural and smooth muscle proteins, and alterations in the deposition of collagen. The purpose of this study was to 1) to create a specific neuropathy in the absence of the additional structural, smooth muscle, and metabolic changes that are induced by partial outlet obstruction; and 2) determine if the contractile dysfunctions induced by the neuropathy have properties similar to the contractile dysfunctions induced by outlet obstruction. In the present study, a progressive "smooth muscle neuropathy" was induced in isolated strips of male rabbit urinary bladder smooth muscle by incubating isolated strips of urinary bladder body in the presence of increasing concentrations of tetrodotoxin (15-1500 nM). In these studies, we determined the effect of increasing concentrations of tetrodotoxin (TTX) on the response to field stimulation utilizing 2 Hz and 32 Hz, at 80 V and 1 ms duration. The effects of TTX on maximum rate of contraction, peak contraction and tonic contraction were monitored. In addition, the effects of atropine (cholinergic muscarinic blockage) and ATP-desensitization (purinergic inhibition) on the effects of TTX were also determined. The results can be summarized as follows: 1) Both atropine and ATP desensitization individually inhibited significantly the peak response to field stimulation. 2) Atropine abolished the tonic response. 3) TTX inhibited the tonic contraction at significantly lower concentrations than it inhibited peak contraction. Thus, at low concentrations of TTX, a condition similar to that seen in obstructive hypertrophy was created. 4) The ED50 in the presence of atropine was significantly greater than the ED50 following ATP desensitization. This may indicate that there are separate synaptic elements for cholinergic and purinergic transmission.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effect of tetrodotoxin on the phasic and tonic responses of isolated rabbit urinary bladder smooth muscle to field stimulation. 143 49

Electrical transmural stimulation evoked contraction and relaxation in isolated urethral circular muscle of the dog. The responses were abolished by tetrodotoxin, indicating their neurogenic origin. The contractile force in the middle urethra was greater than that in the proximal and distal urethra. The contractions were not affected by atropine and propranolol, but were completely inhibited by phenoxybenzamine, prazosin and guanethidine. In preparations contracted with prostaglandin F2 alpha, electrical stimulation induced frequency-dependent relaxation in all urethral portions. Atropine, phenoxybenzamine, prazosin and guanethidine had no effect on the relaxation, while propranolol slightly attenuated the relaxation induced at the highest frequency used (5 Hz). The non-adrenergic, non-cholinergic relaxation was also not affected by ketanserin, methysergide, diphenhydramine, alpha,beta-methylene ATP or capsaicin. Exogenously applied phenylephrine and clonidine both produced contractions but the maximal response to clonidine was much smaller than that to phenylephrine. Acetylcholine produced no or feeble contractions. In the preparations contracted with prostaglandin F2 alpha, isoproterenol and vasoactive intestinal polypeptide (VIP) produced relaxation. These results suggest that the circular muscle of dog urethra is reciprocally innervated by sympathetic adrenergic and non-adrenergic, non-cholinergic nerves, and that the neurogenic responses are markedly affected by muscle tension and the portion of the urethra examined.
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PMID:Neurogenic responses of urethra isolated from the dog. 149 46

Alpha, beta-Methyleneadenosine 5'-triphosphate (alpha, beta-mATP) produced transient contraction of strips of bladder taken from rabbits or guinea pigs, and mechanical responses to field stimulation at 5-100 Hz were reduced by this drug by 5-20%. Atropine reduced responses by approximately 50%, and both drugs together by 80-95%. In double sucrose gap experiments on the rabbit bladder, alpha, beta-mATP selectively reduced but did not abolish an initial excitatory junction potential (ejp), and atropine selectively abolished a late depolarization. In the guinea pig, a single ejp was partially inhibited by either alpha,beta-mATP or atropine. Residual responses were further reduced by tetrodotoxin in both species. The initial ejp and late depolarization in the rabbit were reduced in parallel by hemicholinium over 2 h, suggesting that release of acetylcholine (ACh) and the second transmitter by nerves may be coupled. ACh but not ATP produced an increase in intracellular concentration of inositol trisphosphate in dispersed smooth muscle cells from the rabbit bladder; ATP but not carbachol produced a small transient current across the cell membrane in this species. It is concluded that ACh mobilizes intracellular Ca2+ for contraction, whereas the effect of ATP is dependent on extracellular Ca2+.
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PMID:Neurotransmission in the urinary bladder of rabbits and guinea pigs. 165 52

1. Contractile responses and acetylcholine release evoked by nicotine in guinea-pig detrusor strips were determined by isotonic transducer and radioimmunoassay, respectively. Nicotine stimulated acetylcholine release and a contractile response in guinea-pig detrusor strips treated with the cholinesterase inhibitor, methanesulphonyl fluoride (MSF). Both actions evoked by nicotine were antagonized by the nicotinic receptor antagonist, hexamethonium but were insensitive to tetrodotoxin. 2. A sympathetic nerve blocker, guanethidine and a tachykinin antagonist, [D-Arg1, D-Pro2, D-Trp7,9, Leu11]-substance P (rpwwL-SP) partially inhibited the acetylcholine release evoked by nicotine to much the same degree. The inhibitory effects of guanethidine and rpwwL-SP on acetylcholine release were significantly greater than corresponding effects on the contraction evoked by nicotine. 3. In preparations treated with rpwwL-SP to block the tachykinin receptors, guanethidine had no effect on the response to nicotine. Conversely, after treatment with guanethidine to block release of a mediator from sympathetic nerve endings, nicotine-induced responses were not affected by rpwwL-SP. 4. Nicotine-induced contraction was reduced to 30% by the muscarinic cholinoceptor antagonist, atropine and completely abolished after desensitization of P2-purinoceptors with alpha,beta-methylene ATP in the presence of atropine. 5. A concentration-contractile response curve to neurokinin A (NKA) was shifted to the left after cholinesterase inhibition with MSF. Atropine abolished the facilitatory effect of MSF and partially inhibited contractions induced by NKA at 100 nM to 1 microM. The contractile responses to substance P methyl ester (SPOMe) and Tyr0-neurokinin B (Tyr0-NKB) were not influenced by MSF or atropine. 6. After desensitization of NK, tachykinin receptors with SPOMe or preincubation with senktide, the cholinergic component of the nicotine-induced contraction was the same as the control value (100%). 7. Our findings give further support to our previous results: nicotine stimulates acetylcholine release in a tetrodotoxin-resistant manner in guinea-pig bladder and acetylcholine release evoked by nicotine is increased by the coordinated action of sympathetic nerves and tachykinin(s). It is suggested that the tachykinin receptor subtype involved in acetylcholine release is NK,.
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PMID:Contrasting effects of tachykinins and guanethidine on the acetylcholine output stimulated by nicotine from guinea-pig bladder [corrected]. 171 27

The cat and the rabbit are two of the most popular models for the study of lower urinary bladder function. The cat has been used extensively for in-vivo studies of spinal and supra-spinal micturition reflexes. In contrast, the rabbit has been used extensively for the in-vitro study of bladder function. In order to determine if the results obtained using one species can be applied to another, we have compared the in-vitro physiology and pharmacology of the cat and rabbit bladder using isolated strips and whole bladder preparations. The results can be summarized as follows: 1) The cat displays significant spontaneous activity during in-vitro cystometry, but the rabbit shows no such activity (whole bladder studies). 2) Although the bladder weights of the cat and rabbit are similar, the rabbit bladder has a capacity three times that of the cat. 3) The maximal response to field stimulation was obtained at one gram of passive tension for the rabbit isolated strips, whereas five grams of passive tension was required for the cat strips. 4) Atropine inhibited the response of isolated strips of cat bladder to field stimulation by approximately 13% whereas the response of rabbit bladder strips was inhibited by approximately 45%. 5) The magnitude of the response of rabbit bladder strips to ATP was similar to the response to field stimulation in the presence of atropine; the response of cat bladder strips to ATP was only 20% of the response of that of the rabbit bladder strips, and approximately 10% of the response of the cat strips to field stimulation in the presence of atropine. 6) Field stimulation produced a 10fold greater rise in intravesical pressure in the cat isolated bladder than in the isolated rabbit bladder; in response to bethanechol, the cat bladder generated a 6-fold greater response than the rabbit bladder. It is clear that the in-vitro pharmacological responses of the cat urinary bladder are qualitatively and quantitatively different from that of the rabbit bladder.
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PMID:Comparative physiology and pharmacology of the cat and rabbit urinary bladder. 196 83

1. The effects of 5-hydroxytryptamine (5-HT) were studied in vitro on bladder and urethral muscle strips from the rabbit. 5-HT produced dose-dependent contraction in the detrusor and urethra. 2. The 5-HT-induced contraction could be dose-dependently inhibited by the 5-HT3 antagonists MDL 72222, ICS 205-930 and BRL 43694. No effect of ketanserin, methysergide or metitepine was observed on the contractile response to 5-HT. 3. Atropine and alpha, beta-methylene ATP both partially blocked the contractile response to 5-HT. Together they caused more inhibition than either alone. 4. Atropine and alpha, beta-methylene ATP also inhibited the contractile response to electrical field stimulation. The 5-HT3 antagonist MDL 72222 had no effect on the contraction to field stimulation. 5. The atropine- and alpha, beta-methylene ATP-resistant components of 5-HT-induced contraction were not affected by the 5-HT1 antagonists metitepine, the 5-HT2 antagonists ketanserin and methysergide or the 5-HT3 antagonists MDL 72222, ICS 205-930 and BRL 43694. 6. Tetrodotoxin, hexamethonium, phentolamine and prazosin had no effect on the contractile response to 5-HT. 7. These results suggest that in the rabbit lower urinary tract (i) there are 5-HT3 receptors, (ii) the contractile response to 5-HT is mediated by presynaptic stimulation, (iii) there is non-adrenergic, non-cholinergic excitatory neurotransmission.
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PMID:Evidence for the presynaptic action of 5-hydroxytryptamine and the involvement of purinergic innervation in the rabbit lower urinary tract. 217 17

1. Strength-duration curves for threshold mechanical responses to single transmural stimuli were identical for rat and guinea-pig detrusor. In both species atropine had no effect on the curves, but the curves were shifted to the right by nerve blockade with tetrodotoxin (TTX), and by blockade of P2-purinoceptors with alpha,beta-methylene ATP (alpha,beta-MeATP). 2. With short duration pulses of 50 V and less, the responses were nerve-mediated. Increase in either the strength or duration of the stimulus caused direct muscle stimulation, resistant to blockade with atropine, TTX and alpha-beta-MeATP. 3. The shape of the contractile response to a single nerve stimulus varied from tissue to tissue. The responses could be mono-, bi-, or multiphasic. Bi- or multiphasic responses were normally seen in tissues which were spontaneously active. The multiphasic nature of the response was enhanced by factors which increased the excitability of the cells and was reduced by factors which decreased the excitability. 4. The frequency-response curves in the rat are similar to those previously obtained in the guinea-pig. Atropine suppresses the high frequency response by 25%, with little effect at low frequencies, whereas desensitization of P2-purinoceptors with alpha,beta-MeATP suppresses the responses maximally at low frequencies but still by 75% at high frequencies. A combination of both drugs eliminates the nerve-mediated responses. 5. It is concluded that the response to a single nerve stimulus is mediated by a non-cholinergic transmitter, through activation of P2-purinoceptors. The possibility that simultaneous release of acetylcholine can modify the excitability of cells and thus the configuration of the response to a single stimulus is discussed.
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PMID:Contractile responses of smooth muscle strips from rat and guinea-pig urinary bladder to transmural stimulation: effects of atropine and alpha,beta-methylene ATP. 233 80


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