Effects of tachykinins and guanethidine on the acetylcholine output stimulated by nicotine from guinea-pig bladder.
Explore the source record for details and available documents.
Acetylcholine↗
Biomedical subjects
M Shinkai
Publications and source records attributed to M Shinkai.
Effect of ageing on response to nicotine in rabbit bronchial preparation.
1. Effect of ageing on the response to nicotine was tested in the bronchial muscle preparations from 5, 13, 100 and 125 week-old rabbits. The pD2 value (potency) of nicotine significantly increased in the preparation from the 125 week-old rabbits. No age-related change was found in the pD2 value of carbamylcholine or pA2 value of atropine. 2. No age-related change in characteristics of nicotine receptors. Choline acetyltransferase activity, the amount of acetylcholine released by nicotine and acetylcholineesterase activity decreased in the preparations from the 125 week-old rabbits. 3. Decrease in the pD2 value of nicotine in the preparation from the older rabbit is due to a decline in choline acetyltransferase activity followed by a reduction in the acetylcholine released, and not to a change in characteristics of nicotine receptors. 4. These results also suggest that enzymes may be influenced more easily with age than drug receptors.
Acetylcholine↗
Contractile responses of rat aorta to phenylephrine and serotonin, and aging.
1. The potency (pD2 value) of phenylephrine increased with age from 3 to 10 weeks, but decreased thereafter from 10 to 80 weeks, while the affinity (pKA value) of phenylephrine to alpha 1-adrenoceptors did not alter with aging. 2. The potency (pD2 value) of serotonin did not alter with aging. 3. There is no significant difference between slopes of regression lines between a cytosolic free Ca2+ level ([Ca2+]i) and tension in the presence of phenylephrine in aorta strips from 10- and 60-week-old rats, suggesting that the sensitivity of contractile system to Ca2+ did not alter with aging. 4. Effect of ryanodine on the transient increase of [Ca2+]i and the followed sustained contraction induced by phenylephrine or serotonin in Ca2+ free solution did not alter with aging.
Aging↗
Contrasting effects of tachykinins and guanethidine on the acetylcholine output stimulated by nicotine from guinea-pig bladder [corrected].
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,.
Acetylcholine↗
[Long-term results of operation in patients with annuloaortic ectasia].
From 1974 to 1990, 24 patients were operated on for annuloaortic ectasia. We chose Bentall's technique for 17 patients with great displacement of coronary ostium, but Cabrol's one for 6 patients since coronary displacement was not great. The hospital mortality was 8.3% (2 deaths). The late mortality has been 5/22 (22.7%). Nevertheless, all the patients employed Cabrol's technique have been free from death, events and reoperation. These results were remarkably better than those of primary isolated AVR. It is considered that poor results were caused not by the operating mode using a composite graft but by the connective tissue disorder as primary pathology of annuloaortic ectasia. We conclude that the patient with annuloaortic ectasia must be observed for a long-term after operation.
Adolescent↗
Effects of chronic nicotine treatment on nicotinic receptors in the rabbit urinary bladder.
Nicotine induced a phasic contraction in the rabbit urinary bladder. The response was abolished by hexamethonium and partially reduced by atropine and capsaicin. Simultaneous atropine and capsaicin treatment did not abolish the contraction. These findings suggest that the response to nicotine is due to acetylcholine, tachykinins, and unknown mediator release. In contrast, nicotine-induced contraction diminished following the chronic nicotine treatment without a change of its pharmacological properties. These results suggest the possibility that chronic nicotine treatment causes a decrease in nicotinic receptor numbers. Therefore, the binding properties of (-)-[3H]nicotine on rabbit urinary detrusor muscle membrane fractions were studied to evaluate the effects of chronic nicotine treatment on nicotinic receptors. Specific (-)-[3H]nicotine binding reached saturation and Scatchard plots were curvilinear, suggesting the existence of two different affinity sites for (-)-[3H]nicotine. Dissociation constants (KD) and maximum binding sites (Bmax) were KD1 = 4.91 +/- 1.88 nM, Bmax1 = 2.42 +/- 0.22 fmol/mg protein and KD2 = 263 +/- 56 nM, Bmax2 = 25.0 +/- 4.3 fmol/mg protein. In urinary bladder membrane fractions from chronic nicotine-treated rabbits, KD and Bmax values were KD1 = 3.96 +/- 0.38 nM, Bmax1 = 1.07 +/- 0.25 fmol/mg protein and KD2 = 249 +/- 12 nM, Bmax2 = 10.8 +/- 1.5 fmol/mg protein. Dissociation constants for both sites following chronic nicotine treatment did not change but maximum binding site numbers for both sites significantly decreased (p less than 0.05). These results suggest that the decrease in contractile response evoked by nicotine after chronic nicotine treatment in rabbit urinary bladder is due to a decrease in numbers of nicotinic receptors.
Animals↗
Characterization of tachykinin receptors in urinary bladder from guinea pig.
The contractile responses to substance P (SP), neurokinin A (NKA), Tyro-neurokinin B (Tyr-NKB), senktide (NK3 receptor selective agonist) and SP methyl ester (SPOMe, NK1 receptor selective agonist) were investigated in detrusor strips from guinea pigs. Except for senktide, all drugs induced a concentration-related contraction with the following rank order of potency: SPOMe greater than SP greater than NKA greater than or equal to Tyr-NKB. After desensitization of NK1 receptors with SPOMe, the rank order of potency was NKA greater than or equal to Tyr-NKB greater than SP greater than SPOMe. Both NK1 and NK2 receptors exist in the detrusor strip from guinea pigs.
Animals↗
Effects of aging on alpha 1-adrenoceptor mechanisms and the inhibitory effect of diltiazem on noradrenaline maximum response in isolated rat aortic preparation.
The effects of aging on alpha 1-adrenoceptor mechanisms in aortic preparations isolated from 3-, 6-, 10-, 18-, and 40-week-old rats were studied and compared with serotonin receptor mechanisms in the same preparations. The potency (pD2 value) of noradrenaline increased with age from 3 to 10 weeks, but decreased thereafter with age from 10 to 40 weeks. The affinity (pKA value) of noradrenaline and of prazosin (pA2 value) did not alter with aging. The change in potency or the pD2 value of noradrenaline was proportional to receptor reserve (pD2-pKA value) for noradrenaline, suggesting that the change of potency of noradrenaline with age was due to a change of receptor reserve, but not to change of drug affinity to alpha 1-adrenoceptors. The potency (pD2 value) and affinity (pKA value) of serotonin, and the affinity (pA2 value) of ketanserin, did not alter with aging, suggesting that serotonin receptor mechanisms in rat aorta did not change with age. The inhibitory effect of diltiazem on noradrenaline maximum response decreased with age from 3 to 10 weeks, but increased with age from 10 to 40 weeks. An inverse relationship between changes of diltiazem inhibition and receptor reserve of noradrenaline was found. Diltiazem's inhibitory effect on serotonin maximum response did not alter with aging.
Aging↗
Pharmacological action of nicotine in the isolated urinary bladder from rabbit: special reference to the chronic nicotine treatment.
1. A mode of action of nicotine and a change of the responsiveness to nicotine following chronic nicotine treatment in the urinary bladder of rabbit were investigated. 2. Nicotine induced only a contraction in the urinary bladder of rabbit, and the response to nicotine was reduced by hexamethonium, atropine and capsaicin. These findings suggest that the contractile response to nicotine was mediated through an action on the nicotinic receptors and partially due to the release of acetylcholine and tachykinins. 3. Tetrodotoxin did not inhibit the contractile response to nicotine in the rabbit detrusor muscle, suggesting that the nicotine-induced response may be produced mainly through a sodium action potential-independent process. 4. Nicotine-induced contraction was reduced following the chronic nicotine treatment without a change of its pharmacological properties. These findings suggest that chronic nicotine treatment might cause a decrease of the amounts of nicotinic receptors and also receptors for mediators released by nicotine.
Animals↗
Mechanism of action of nicotine in isolated iris sphincter preparations of rabbit.
1. Nicotine produced a transient contraction of rabbit isolated iris sphincter muscle, a parasympathetic ganglion-free tissue. The response to nicotine was antagonized by hexamethonium, but was insensitive to tetrodotoxin (TTX). While single treatments with atropine, capsaicin or [D-Arg1, D-Pro2, D-Trp7,9, Leu11]-substance P (rpwwL-SP) partially blocked the response, combined treatment abolished it. 2. Chronic treatment of animals with nicotine added to the drinking water (about 12 mg kg-1 per day) had no effect on the responsiveness to nicotine or the pharmacological properties of nicotine-induced contraction. 3. These results suggest that acetylcholine and tachykinin(s) released via sodium channel-independent mechanisms from nerve terminals of parasympathetic and primary sensory nerves, respectively, are involved in the nicotine-induced contractile response.
Animals↗
Mechanism of action of nicotine in isolated urinary bladder of guinea-pig.
1. Nicotine produced a transient contraction of isolated strips of guinea-pig urinary bladder. The response to nicotine was antagonized by the nicotinic receptor antagonist, hexamethonium but was insensitive to tetrodotoxin. 2. The nicotine-induced contraction was potentiated by the cholinesterase inhibitor, physostigmine, and was reduced to 50% and 70% by the muscarinic cholinoceptor antagonist, atropine and the sympathetic neurone blocking drug, guanethidine, respectively. Chemical denervation with 6-hydroxydopamine abolished the inhibitory effect of guanethidine. Simultaneous treatment with atropine and guanethidine did not abolish the response to nicotine, but the degree of inhibition was comparable to that obtained with atropine alone. 3. The nicotine-induced contraction was insensitive to bunazosin and yohimbine (alpha 1- and alpha 2-adrenoceptor antagonists, respectively), and exogenously applied noradrenaline did not cause a contraction even in the presence of blockade of noradrenaline uptake mechanisms with desipramine and normetanephrine and of beta-adrenoceptors with propranolol, suggesting a non-adrenergic nature of the sympathomimetic effect of nicotine in this tissue. 4. The nicotine-induced contraction in the presence of atropine was abolished after desensitization of P2-purinoceptors with alpha, beta-methylene adenosine 5'-triphosphate, a slowly degradable ATP analogue selective for P2-purinoceptors. By this desensitization, the response to ATP, but not to histamine, was also abolished. 5. A cyclo-oxygenase inhibitor flurbiprofen partially inhibited the nicotine-induced contraction. The degree of the inhibition was more pronounced in the presence of atropine than in its absence. Flurbiprofen antagonized the response to exogenously applied ATP in an unsurmountable manner, but not that to carbachol. 6. The present results suggest that nicotine might induce a contraction through an interaction with nicotinic receptors located on the terminals of, possibly, (i) parasympathetic cholinergic, (ii) sympathetic non-adrenergic and (iii) non-sympathetic purinergic nerves in guinea-pig detrusor preparations, and that a portion of the contraction due to the purine nucleotide released is possibly potentiated by intramural prostaglandin(s). Parasympathetic cholinergic output might be modulated by an unknown excitatory substance released by nicotine from sympathetic nerve. 7. Nicotine reveals a latent excitatory effect of the sympathetic hypogastric nerve which innervates guinea-pig detrusor.
Animals↗
[Guidance and nursing of a patient with acute myocardial infarction and senile dementia: a case study].
Explore the source record for details and available documents.
Aged↗
[A case of hereditary spherocytosis associated with cholelithiasis in a 6-year-old boy].
Explore the source record for details and available documents.
Child↗
Recovery of end-stage organ dysfunction by circulatory assist.
To clarify the effectiveness of left ventricular assist on recovery of critical organ dysfunction, 18 patients with ventricular septal rupture or free wall rupture after acute myocardial infarction were retrospectively studied. Fifteen patients were managed with an intraaortic balloon pump (IABP group), and three with a left ventricular assist device (LVAD group) after surgery. In the IABP group, nine patients survived and six died. There were no significant differences between survivors and nonsurvivors with respect to age, cardiopulmonary bypass time, or preoperative renal function. In addition, there were no significant differences in the early postoperative changes in cardiac index. Larger doses of catecholamines were required in nonsurvivors than in survivors, however; blood urea nitrogen and creatinine levels were significantly higher in nonsurvivors than in survivors, and the nonsurvivors' creatinine clearance values stayed under 20 ml/min during the postoperative course, so that all nonsurvivors required renal assist. All in the LVAD group were weaned. Two patients were lost, however, because of cardiac arrythmia and massive gas embolism. Cardiac index in the LVAD was maintained at over 2.1 L/min/m2 with a minimum dose of catecholamines, regardless of poor left ventricular function, and creatinine clearance recovered to over 20 ml/min during circulatory assist. From these data, high doses of catecholamines depressed renal function after surgery. Therefore, it has been concluded that the major role of circulatory assist is to maintain more of the physiologic circulation with minimum doses of drugs.
Aged↗
Mechanism of action of nicotine in isolated urinary bladder of guinea-pig: involvement of tachykinin(s) released by nicotine in the drug's sympathomimetic effect.
A sympathetic neurone blocking drug, guanethidine, and a tachykinin antagonist, [D-Arg1, D-Pro2, D-Trp7,9, Leu11]-substance P (rpwwL-SP), partially inhibited the contractile response to nicotine to the same degree in the isolated detrusor strips of guinea-pig urinary bladder. Application of rpwwL-SP completely abolished the inhibitory effect of guanethidine on the nicotine-induced contraction, suggesting that the tachykinin(s)-ergic transmission might be involved in the sympathomimetic effect of nicotine. Conversely, when the preparation was treated with guanethidine to block release of a mediator from the sympathetic nerve, the inhibitory effect of rpwwL-SP was diminished, suggesting an exclusive contribution of the sympathetic nerve communications to the action of the tachykinin(s). We previously suggested that nicotine may release acetylcholine and ATP to contract the detrusor strips, and that acetylcholine output may be increased by an unknown substance released from the sympathetic nerve by nicotine. In preparations treated with atropine, rpwwl-SP had no effect on the nicotine-induced contraction. The concentration-response curves for carbachol and ATP were not influenced by rpwwl-SP. After tachyphylaxis to capsaicin developed, the nicotine-induced contraction was not affected. It is suggested that in guinea-pig detrusor, tachykinin(s) from capsaicin-insensitive sites is (are) involved in the excitatory sympathomimetic effect of nicotine, and that the tachykinin(s) behave(s) as a modulator finally to increase the acetylcholine output from the parasympathetic cholinergic nerve.
Adenosine Triphosphate↗