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Biomedical subjects

M Papasova

Publications and source records attributed to M Papasova.

At least 37 records · Page 2Linked to original sources

A new analogue of substance P with antagonistic properties in renal and pulmonary arteries.

The effects of a new analogue of substance P (SP-A) and its interaction with substance P (SP) were studied in vitro isolated preparations from rabbit renal arteries and rat renal and pulmonary arteries. SP-A in did not affect the resting tone and the contractions of the rabbit renal arteries, evoked by field electrical stimulation (FES) but dose-dependently (10(-10)M - 5 X 10(-8)M) antagonized the inhibitory effects of SP on the FES-provoked contractions, the antagonism being of a non-competitive type. In the rat renal arteries SP had two different effects--depression of the FES-evoked contractions, and increase of the resting tone. SP-A did not exert per se effects on the tone and on the electrically-provoked contractions in these arteries. SP-A non-competitively antagonized both actions of SP in the same vessels. In rat pulmonary arteries SP increased the resting tone, whereas SP-A did not affect the resting tone and the FES-induced contractions. SP-A non-competitively antagonized the tone-increasing action of SP. The new analogue of SP may be useful in studying the mechanism of action of SP and its role in physiological and pathological reactions.

Animals↗

Electromechanical coupling in cat stomach smooth muscle in Ca2+-free EGTA-containing solutions.

The electromechanical coupling in the smooth muscles of cat stomach was studied in Ca2+-free solutions containing EGTA. The experiments were carried out on circular muscle strips from the corpus of cat stomach using the single sucrose gap technique. Complete disappearance of the spontaneous electrical and contractile activity of the muscle strips was observed in Ca2+-free solution. Addition of EGTA (0.1 to 1 mM) to the Ca2+-free solution caused a considerable depolarization of the membrane and appearance of fast fluctuations of the membrane potential, grouped in periodically appearing spindles. After 10-15 min the fluctuations of the membrane potential obtained the shape of flat plateau-like waves. This electrical and contractile activity was completely eliminated by Mn2+ (2.5 mM), D600 (10(-6) M) or nifedipine (10(-8) M). Light inactivation of nifedipine-induced restoration of the chelator-evoked potentials and their reduction to the initial values. The chelator-induced electrical activity depended on the concentration of extracellular Na+, and it was not recorded when the Na+ concentration was decreased below 60 mM. These results support the assumption that the chelator-induced flat plateau-like waves are determined by Na ions penetrating through the Ca-channels. These potentials, appearing in Ca2+-free EGTA-containing solution, probably cause the release of Ca2+ from the intracellular stores in amounts sufficient for the realization of the electromechanical coupling.

Animals↗

Changes in the electrical activity of the stomach after partial resection of the pancreas and occlusion of the pancreatic duct.

The electrical activity of the stomach and duodenum of six mongrel dogs was studied under chronic conditions after partial resection of the pancreas and occlusion of the pancreatic duct. Changes in the electrical activity were observed only in the stomach, manifested in the form of groups of slow potentials with accelerated rhythm (over 7 cpm--tachygastria) or delayed rhythm (below 3 cpm--bradygastria). A definite dynamics was observed in the appearance and development of rhythmic disorganization. The duration of the groups of slow potentials with abnormal rhythm increased 10-12 days after surgery. Radioimmunological studies showed a postoperative increase in the glucagon level, paralleled by a decrease in the content of the C-peptide and insulin in the blood plasma. Influsion with insulin (0.5 IU i.v.) regulates the disorganized antral rhythm. The dysbalance in the insulin/glucagon ratio in the blood serum is assumed to be the probable mechanism of the rhythmic disturbances.

Animals↗

Effects of substance P on isolated preparations from rabbit and rat renal arteries.

Substance P (SP) increased the tone of isolated ring preparations from renal and pulmonary arteries from rat but not from rabbit. Indomethacin decreased the amplitude of SP-evoked tone by 50%. SP inhibited in a dose-dependent manner the electrically-evoked contractions of the rabbit and rat renal arteries. The threshold concentrations producing inhibitory effects of SP were 10(-12) M for rabbit arteries and 10(-9) M for rat arteries. The maximal inhibition was observed at 10(-8) M and 10(-6) M, respectively. In the renal arteries of spontaneously hypertensive rats SP potentiated the electrically-evoked contractions. SP caused relaxation of the rabbit renal arteries, previously contracted with noradrenaline (10(-7) M), high [K+]0 (30 mM) and prostaglandin F2 alpha (10(-6) M). The results have shown that the effects of SP on the arterial contractions depend on the species and on the normal or pathologic conditions. A direct action of SP on the arterial muscle cells is suggested.

Animals↗

Participation of cholinergic mechanisms in the realization of the effect of bombesin on the migrating myoelectrical complex.

The experiments were carried out on dogs with chronically implanted bipolar ball-shaped silver electrodes in the antral part of the stomach and duodenum. The effect of bombesin (injected intravenously in a dose of 200 ng/kg) on the migrating myoelectrical complex (MMC) was examined after pretreatment with hexamethonium (10 mg/kg) or atropin (100 micrograms/kg), or alpha-antagonists (phentolamine, 2 mg/kg) and beta-antagonists (propranolol, 2 mg/kg) of the adrenergic receptors. Introduced during the second MMC phase, bombesin caused inhibition of the spike activity, accompanied by an increase of the slow potential frequency. Prolonged intensified spike activity occurred 5-10 min later. Early brief appearance of spike potentials was observed after bombesin in the presence of hexamethonium, which was not manifested on the background of atropin. After hexamethonium or atropin, however, the phase of the late activation of the spike activity did not occur and there was no change in the effect of bombesin on the frequency of the slow potential. The alpha- and beta-antagonists of the adrenergic receptors do not change the effect of bombesin on the electrical activity of the stomach and the intestines.

Animals↗

Bombesin-induced changes in membrane potential-dependent phasic contractions of cat gastric muscle.

Electrical and contractile activities of smooth muscle strips isolated from the circular muscle layer of cat gastric antrum were studied using the sucrose gap technique. Bombesin (10(-8) mol/l) depolarized the gastric muscle; this was accompanied by an increase in the strip tone, in the plateau action potential frequency and in both the frequency and the amplitude of the spike potentials as well as by a shortening of the plateau action potential duration. Both the frequency and the amplitude of the phasic contractions increased thereafter. The changes in the frequency of the plateau action potentials and contractions were not influenced either by antagonists of cholinergic and adrenergic receptors or by TTX. In the presence of the Ca antagonists D600 (10(-6) mol/l) and nifedipine (10(-7) mol/l) or in Ca-free medium containing EGTA the effect of bombesin on the frequency of the plateau action potentials and phasic contractions remained unchanged; however, spike potentials were not observed and no increase in the amplitude of phasic contractions occurred. UV-light inactivation of nifedipine restored the typical bombesin effect on the electrical and contractile activities of the gastric smooth muscle. The present data suggest that the effect of bombesin on the frequency of both plateau action potentials and phasic contractions is not linked with Ca2+ influx.

Action Potentials↗

Responsiveness to noradrenaline of longitudinal and circular smooth muscles of cat caecum during the postnatal period.

1. The changes in the responsiveness of the isolated longitudinal and circular smooth muscles from cat caecum to adrenergic agents during the postnatal period were studied by the effect of noradrenaline (0.01-100 mumol) on the smooth muscle tone and phasic contractions. 2. Noradrenaline (10 mumol) contracted the preparations of longitudinal and circular muscles isolated from cats between 15 and 60 days postnatal via stimulatory alpha 1-adrenoceptors. 3. Noradrenaline applied cumulatively (0.01-100 mumol) produced a concentration-determined but age-independent inhibitory effect on the phasic contractions of longitudinal muscle and exercised a concentration- and age-determined effect on the phasic activity of circular muscle. 4. The adrenoceptors of cat caecum are not differentiated until 60 days postnatal.

Animals↗

Leucine-enkephalin as a modulator of neurotransmission in cat lower esophageal sphincter.

Interactions between cholinergic, adrenergic and noncholinergic nonadrenergic inervation in lower esophageal sphincter determine the character of smooth muscle responses to field electrical stimulation. The neurogenic responses of muscle strips from the proximal (LES1), middle (LES2) and lower (LES3) parts of lower esophageal sphincter (LES) are: primary relaxation and secondary contraction in LES1, relaxation in LES2 and primary contraction followed by primary relaxation in LES3. Leucin-enkephalin in concentration of 0.1 microM and 1 microM leads to: increasing of amplitude of the primary relaxation and inhibition of secondary contraction in LES1, enhancing of amplitude of relaxation in LES2 and converts the response in LES3 from two into three component one so that the primary relaxation and the primary contraction are followed by secondary poststimulation relaxation. These effects are most probably the results of inhibition of noradrenaline and acetylcholine releasing under the influence of leucine-enkephalin and of alteration of the correlation between the neurotransmitters. It is assumed that Leucine-enkephalin operates in LES as a neuromodulator inhibiting both the adrenergic and cholinergic neurotransmission.

Animals↗

Postnatal development of responsiveness to adrenergic agents of longitudinal and circular smooth muscles from cat terminal ileum.

The changes in the responsiveness of the isolated longitudinal and circular smooth muscles from cat terminal ileum to adrenergic agents during the postnatal period were studied by the effect of noradrenaline (0.01-100 mumol) on the smooth muscle tone and phasic contractions. Cumulatively applied noradrenaline (0.01-10 mumol) decreased the longitudinal muscle tone without age-dependent differences via inhibitory alpha 1-adrenoceptors. Noradrenaline decreased the phasic contraction amplitude of longitudinal muscle via inhibitory alpha 1-adrenoceptors. Cumulatively applied noradrenaline (0.01-10 mumol) exerted an age-dependent effect on the circular muscle tone via stimulatory alpha 1-adrenoceptors. alpha 1-adrenoceptors continue to develop functionally at 60 days postnatal. Noradrenaline decreased the phasic contraction amplitude of the circular muscle and exerted a stimulant effect on the tone which suggested an existence of two alpha 1-adrenoceptor subtypes.

Age Factors↗

Changes in the reactivity of the intrinsic nervous system of the stomach to hexamethonium after transthoracic vagotomy.

Experiments were carried out on seven breedless dogs with chronically implanted electrodes in the stomach. The effect of hexamethonium (in doses of 0.2, 0.3, 0.5, 1, 2, 3, 5, 7 and 10 mg/kg, i. v.) on the migrating myoelectrical complex (MMC) was studied before and after transthoracic vagotomy. Injected on the background of the first MMC phase, hexamethonium in doses of up to 2 mg/kg induces the appearance of spike potentials (SP). Applied on the background of spike activity, hexamethonium induces the appearance of spike activity of the type of the 3rd MMC phase. In a dose exceeding 2 mg/kg, introduced during SP activity, hexamethonium interrupts for different periods of time the SP generation and shortens the duration of the active MMC phases. On the background of increased spike activity characteristic of the stomach after vagotomy, 3 mg/kg hexamethonium have almost no effect on the electrical activity, whereas 10 mg/kg only reduce the percentage of slow waves accompanied by SP. It is probably that after vagotomy the excitability of the intrinsic nerve cells is increased, therefore even the high doses of the ganglionic blocker hexamethonium cannot inhibit entirely the active phases of MMC.

Animals↗

4-Aminopyridine-induced changes in the electrical and contractile activities of the gastric smooth muscle.

Effects of 4-aminopyridine (4-AP) on the electrical and contractile activities of the fundus and antrum of the cat stomach were studied using the sucrose-gap technique. In the fundus, low concentrations of 4-AP (up to 1 mmol/l) induced membrane depolarization and appearance of spike potentials and phasic contractions. After preliminary administration of atropine, 4-AP produced an opposite effect: hyperpolarization and relaxation. On the background of tetrodotoxin (TTX) plus antagonists of cholinergic and adrenergic receptors, high concentrations of 4-AP (greater than 5 mmol/l) caused membrane depolarization and appearance of spike potentials and phasic contractions. In the antrum, 4-AP in low concentrations (up to 1 mmol/l) decreased both the amplitude and the duration of the second component of the plateau-action potential, as well as those of the phasic contractions. This effect decreased in the presence of adrenergic receptor antagonists and was abolished by TTX. On this background, high concentrations of 4-AP (greater than 5 mmol/l) led to the appearance of spike potentials superimposed on the second component of the plateau-action potentials, and to a further increase in the phasic contraction amplitudes. The present data suggest that 4-AP exerts its effects via an increase in neurotransmitter release (low concentrations) and/or directly on the smooth muscle cell membrane (high concentrations).

4-Aminopyridine↗

Changes in the migrating myoelectrical complex of canine gastro-intestinal tract depending on the dietary regime.

Experiments were made to study the effect of vegetable protein (soya) and animal protein (meat) on the migrating myoelectrical complex (MMC) in the stomach and small intestine of dogs with chronically implanted electrodes. MMC was tested under different dietary conditions: (1) Diet No 1 comprising animal protein; (2) Diet No 2 poor in protein and diet No 3 with vegetable protein (soya). In the case of protein-deficient dietary regime (diet No 2) disturbance in MMC is observed--spike activity is constantly recorded. First phase of MMC is not observed. The transition from diet No 2 to diet No 3 at the end of the first week is accompanied by a tendency toward the formation of brief rest periods, with a considerable increase in the duration of 100% spike activity. At the end of the 30th day the different MMC phases were not well differentiated. Upon transition from protein-poor regime to diet No 1 during the second week, the different MMC of the stomach and small intestine are very well expressed. The problem of the generation and propagation of MMC is discussed. MMC is considered as a manifestation of the "biological clock" which responds to every change taking place in the organism during its interaction with the environment.

Action Potentials↗

Development of innervation in cat gastrointestinal sphincters during the postnatal period. (Functional studies).

The development of function in the intramural nerves was investigated by evaluating the mechanical responses of the smooth muscle of cat gastrointestinal sphincters to transmural electrical stimulation (2-20 Hz, 0.5 msec, supramaximal intensity for 20 sec) between 1 and 60 days postnatal. The intramural nervous system of the gastrointestinal sphincters was found to develop functionally in a cranio-caudal sequence. The cholinergic innervation in the lower esophageal sphincter (LES) was well developed in the first postnatal days. The development of the non-cholinergic, non-adrenergic innervation, however, proceeded further. An age-determined increase in the amplitude of the adrenoblocker-resistant primary relaxation of LES evoked by switching on the electrical stimulation, was established. The cholinergic innervation in the pyloric sphincter (PS) and ileocecal sphincter (ICS) was developed in the first postnatal days. The non-cholinergic, non-adrenergic innervation appeared in PS between 10- and 15-days postnatal and in ICS between 15- and 60-days postnatal. Noradrenaline (1 mumol) elicited responses typical of adult cats as early as the first postnatal days: contraction in LES and relaxation in PS. In ICS it did not evoke the typical response, contraction, until 15 days after birth.

Age Factors↗

Changes in the responsiveness of the cat ileocecal sphincter to adrenergic agents during the postnatal period.

The changes in the responsiveness of the cat ileocecal sphincter (ICS) to adrenergic agents during the postnatal period were studied by the effect of noradrenaline (applied cumulatively: 0.01-100 mumol) on the mechanical activity:smooth muscle tone and phasic contractions. Noradrenaline contracted the ICS smooth muscle through alpha 1-adrenergic receptors. These receptors were differentiated in the first postnatal days but continue to develop functionally even after 60 days postnatal. An age-determined decrease in the EC50 values of noradrenaline, inducing tonic contractions, was established. Noradrenaline inhibited the phasic contractions of ICS. This effect increased after beta-adrenergic receptor blockers, and disappeared after blocking of alpha 1-adrenergic receptors, which suggests the existence of a postjunctional inhibitory adrenergic receptor of alpha 1 type. The beta-adrenergic receptors in the ICS smooth muscle are not differentiated until 15 days postnatal. They developed functionally towards 30 days postnatal.

Adrenergic Fibers↗

Neurotransmitter interactions in smooth muscles from cat internal anal sphincter (in vitro experiments).

The contractile activity of strips (15 X 2 mm) isolated from cat internal anal sphincter (IAS) has been studied under isometric conditions. Noradrenaline (above 10(-10) mol/l) induces contraction of IAS, antagonized by phentolamine. Isoprenaline (10(-8)-10(-5) mol/l) has no effect on IAS. Acetylcholine and carbachol (above 10(-6) mol/l) result in relaxation of the IAS preparations, which is blocked only by simultaneous administration of atropin (10(-6) mol/l) and hexamethonium (10(-4) mol/l). The acetylcholine-induced relaxation is not influenced by guanetidine and reserpine, but it is antagonized by tetrodotoxin (TTX) (10(-7) g/ml). Nicotine (10(-6)-10(-4) mol/l) also causes IAS relaxation which is not influenced by atropin, being blocked by hexamethonium and antagonized by TTX. The IAS relaxation induced by acetylcholine and nicotine is not associated with adrenergic mechanisms; it is assumed to be the result of a release of noncholinergic, nonadrenergic inhibitory neurotransmitter by means of presynaptic postganglionic cholinergic receptors. Data are also presented concerning the release of noradrenaline through presynaptic N-cholinergic receptors, when nicotine and high acetylcholine concentrations are applied after treatment of the preparations with scorpion venom or after increasing the K+-concentration in the nutrient solution to 16-20 mmol/l. The complex neurotransmitter interactions at IAS level are discussed.

Anal Canal↗

Modulation of the release of noradrenaline and of noncholinergic, nonadrenergic inhibitory neurotransmitter through presynaptic N-cholinergic receptors by means of depolarizing agents in cat internal anal sphincter.

The contractile activity of smooth-muscle strips (15 X 2 mm), isolated from the internal anal sphincter [IAS] of chloralose-anaesthesized cats, was recorded under isometric conditions. The relaxation effects of exogenously applied acetylcholine (Ach) and nicotine (Ns on cat IAS turn into contractile after treatment of the preparations with depolarizing agent (increased [K+]0 scorpion venom, ouabaine). These contractile effects are blocked completely by phentolamine, guanetidine, hexamethonium and they are antagonized by TTX. Relatively high N concentrations induce a three-phase effect whose second contractile component is phentolamine- and guanethidine-sensitive. Field electrical stimulation (FES - 0.7-20 Hz, 0.1 ms, 40 V, duration 15 s) induces biphasic response in IAS: initial contraction which increases after an increase in [K+]0 and is blocked by phentolamine and guanethidine, with subsequent relaxation which is not affected by adrenergic and cholinergic blockers. The effects of FES are TTX-sensitive. The article discusses the problem of the release of noncholinergic nonadrenergic inhibitory neurotransmitter and of noradrenaline by means of presynaptic N-cholinergic receptors. It is assumed that the correlation in which the two transmitters are released depends on the different threshold value of the membrane potential of the nerve terminals, whereby excitatory-secretion coupling takes place.

Acetylcholine↗

Electrical activity of the stomach: nervous control.

The role of the extramural vagus nerves in the modulation of gastric electrical activity and the myoelectrical complex (MEC) was studied by electrical stimulation of the nerve of Latarjet. As a consequence of the interruption of vagal impulses for five months by bilateral transthoracic vagotomy, the intramural nervous system began to perform as an organiser and modulator of the disorganised gastric electrical activity. The modulating role of the intramural nervous system was also demonstrated by stimulating the transmural electrical system, using parameters such as spike-firing and duration of stimulation of the MEC, and by blocking the adrenergic receptors.

Action Potentials↗

Ionic interactions in the smooth muscles of cat pulmonary artery and portal vein.

The contractile activity of isolated smooth-muscle preparations of pulmonary artery and portal vein was recorded under isometric conditions and the changes in the membrane potential were recorded by the sucrose gap method. The replacement of Na+ by sucrose or cholinechloride ([Na+]o = 0) in the presence of phentolamine and atropine causes contraction of the smooth-muscle strips, characterized by initial fast and subsequent slow tonic component. The contraction is accompanied by hyperpolarization of the membrane. D600 (10(-5) M) and sodium nitroprusside (10(-5) M) do not influence the tonic component of the [Na+]o = 0-induced contraction. Low Na-content in the solution ([Na+]o = 15.5 mM) causes brief contraction only of the portal vein strips. In Ca-free solution the tone of the arterial preparations does not change, while the tone of portal vein strips decreases and phasic contractions are inhibited. In Ca-free solution or after pretreatment of the strips with 10 mM LaCl3, substitution of sodium induces a slowly developing contraction without initial fast component. Pretreatment of the preparations with ouabain (10(-4) M) or their preincubation in K-free solution potentiates the [Na+]o = 0-induced contraction. The results obtained exclude membrane-potential-dependent processes in the development of the [Na+] o = 0-induced contraction and support the existence of Na+-Ca2+ exchange mechanism in the smooth muscles of cat pulmonary artery and portal vein.

Animals↗