Biomedical subjects

A Den Hertog

Publications and source records attributed to A Den Hertog.

At least 37 records · Page 2Linked to original sources

PubMed1988

The prostaglandin response in guinea-pig taenia caeci and trachea smooth muscle of different ages.

The concentration-response curves for the carbachol-induced contraction of smooth muscle cells of guinea-pig taenia caeci and trachea were not dependent on tissue age. The prostaglandin E2 and F2 alpha responses increased with age in taenia caeci in contrast with the PGE2 response evoked in trachea. The high-potassium responses evoked in taenia caeci and trachea both increased at higher tissue age. Methoxyverapamil only inhibited the age-dependent responses. The results suggest that it is mainly the voltage-dependent calcium channels that are involved in the age-dependent prostaglandin response.

Aging↗

PubMed1987

Desensitization of PGE2 and PGI2 induced contractions in different smooth muscles of guinea-pig unmasking relaxing properties of prostanoids.

Prostaglandin E2 (PGE2) and 16,16-dimethyl PGE2 (16,16-dm PGE2) caused contraction of guinea-pig taenia caeci, contraction and at higher concentrations relaxation of trachea and relaxation of ureter smooth muscle. The prostacyclin derivative iloprost induced contraction of taenia caecum, while it was inactive in the other preparations. After pretreatment of the smooth muscles with 16,16-dm PGE2, stimulation of the PGE2 receptors in taenia caeci and trachea and of PGI2 receptors in taenia caeci caused relaxation. The results indicate that the prostanoid receptor mediating contraction is selectively vulnerable for desensitization in contrast with the receptor mediating smooth muscle relaxation.

16,16-Dimethylprostaglandin E2↗

PubMed1987

The action of some new aminopyridines on mammalian non-myelinated nerve fibres.

The effects of a recently synthesized series of aminopyridines 2-methyl-4-AP, 2-chloro-4-AP and 2-(N,N-methyl-benzyl)amino-4-AP (2A-7) on voltage-operated sodium and potassium channels and on the sodium pump activity of non-myelinated fibres of the guinea-pig vagus nerve were studied with the sucrose-gap method. The compound action potential evoked by electrical stimulation and the propagation velocity along the nerve were not affected by 2-methyl-4-AP or 2-chloro-4-AP up to a concentration of 10(-3) M. The post-tetanic potential (PTH) evoked by repetitive stimulation of the nerve and reflecting sodium pumping was also not affected by these agents. The amplitude and duration of the compound action potential were enhanced to some extent by 2-methyl-4-AP at the highest concentration used (3 X 10(-3) M); this action was also observed and was more pronounced with 4-aminopyridine (4-AP). The other aminopyridine 2A-7 (3 X 10(-5) - 3 X 10(-4) M) caused suppression of the compound action potential, a diminished propagation velocity and a reduction of the PTH, an action also observed with lidocaine. These results show that 2-methyl-4-AP and 3-chloro-4-AP did not affect the voltage-operated sodium or potassium channels in non-myelinated fibres of the vagus nerve. Only 2-methyl-4-AP had a small 4-AP-like action at high concentrations. The aminopyridine 2A-7 possesses a local anaesthetic action as reflected by the inhibition of voltage-operated sodium channels.

Action Potentials↗

PubMed1987

The action of prostaglandins on ureter smooth muscle of guinea-pig.

Prostaglandins of the E type (PGE) relaxed guinea-pig ureter but prostaglandins of the F type (PGF) did not affect smooth muscle contraction. Hyperpolarization and relaxation of the muscle cells caused by the PGEs were achieved at concentrations in a different range, a feature also observed in the presence of forskolin or iso-butyl-methyl-xanthine (IBMX). Hyperpolarization was inhibited in the presence of k-strophanthoside. The c-AMP content of ureter smooth muscle cells was increased in the presence of PGE2. These observations suggest that the PGE-induced hyperpolarization is caused by activation of the sodium-potassium pump and that enhancement of the cellular c-AMP level plays a major role in the PGE-induced relaxation.

1-Methyl-3-isobutylxanthine↗

PubMed1987

The action of mebeverine and metabolites on mammalian non-myelinated nerve fibres.

The effect of mebeverine, mebeverine-alcohol and veratric acid on voltage-operated ion channels and on sodium pump activity were studied. The amplitude and duration of the compound action potential evoked in the vagus nerve were decreased by mebeverine but not by the metabolites. The amplitude of the post-tetanic hyperpolarization was decreased by mebeverine while the time constant of decay, representing sodium-potassium pump activity, was not affected by the compounds tested. These results show that mebeverine exerts a local anaesthetic action by blocking voltage-operated sodium channels.

Action Potentials↗

PubMed1987

Modification of alpha 1-receptor-operated channels by mebeverine in smooth muscle cells of guinea-pig taenia caeci.

Changes in the potential and contractility of smooth muscle cells of guinea-pig taenia caeci were measured (22 degrees C) in order to investigate the effect of mebeverine, a derivative of beta-phenylethylamine, on alpha 1-receptor-operated ion channels in particular. Mebeverine (6 X 10(-6) M) showed atropine-like properties by shifting to the right the concentration-response curve obtained with carbachol. Hyperpolarization and cessation of spike activity of the muscle cells, accompanied by an increased amplitude of the electrotonic potential were observed in the presence of mebeverine (6 X 10(-5] after block of the alpha 2-, beta- and muscarinic receptors. This effect of mebeverine was not observed in low-sodium solution (23.8 mM), suggesting that mebeverine decreased sodium permeability. The alpha 1-receptor-induced hyperpolarization caused by adrenaline (3 X 10(-6) M) in the presence of mebeverine declined after reaching an initial maximum. The hyperpolarization induced by a second addition of adrenaline to the preparation was decreased and sustained in the presence of mebeverine, while the decrease of the electrotonic potential evoked during the alpha 1 response was less pronounced. The transient hyperpolarization representing the alpha 1 response in the absence of extracellular calcium developed more slowly in the presence of mebeverine, the area of the response being constant. When the experiment was continued in calcium-free solution after a short exposure to calcium-containing Krebs solution still in the presence of mebeverine, the alpha 1-receptor-induced hyperpolarization was suppressed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

The action of procainamide and quinidine on the alpha 1-receptor-operated channels in smooth muscle cells of guinea-pig taenia caeci.

The effect of procainamide (2.0-5.0 mM) and quinidine (0.2-1.0 mM) on the alpha 1 response evoked by adrenaline (3 X 10(-6) M) in smooth muscle cells of guinea-pig taenia caeci (22 degrees C) was studied in the presence of yohimbine (3 X 10(-6) M), propranolol (3 X 10(-6) M) or atropine (10(-6) M). The electrotonic potential elicited by the application of a constant current to the preparation was slightly increased (about 10%) by procainamide (5.0 mM) but not by quinidine (1.0 mM). The double-sucrose gap method was used for measurements. The alpha 1 response evoked by adrenaline in the absence of extracellular calcium (15 min) was represented by a transient hyperpolarization of the muscle cells, while the hyperpolarization elicited in the presence of calcium was sustained. The hyperpolarization is caused by enhancement of the potassium efflux assumed to be linked with mobilization of calcium form a cellular structure. Superfusion of the preparation with calcium-containing solution to replenish the calcium store in the presence of procainamide (10 min) before the alpha 1 response evoked in the absence of calcium and procainamide did not affect the transient hyperpolarization. Quinidine, however, suppressed the alpha 1 response when the same procedure was followed. Both the transient and the sustained hyperpolarization evoked in smooth muscle cells in the presence of procainamide (15 min) or quinidine in calcium-containing or in calcium-free solution, respectively, were inhibited. The alpha 1 response was reflected by a depolarization of the muscle cells after the potassium channels had been blocked with apamin (3 X 10(-7) M, 20 min).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Changes in membrane potential and phosphoinositides during alpha 1-adrenoceptor stimulation in smooth muscle cells of guinea-pig taenia caeci.

The effect of a submaximal concentration of adrenaline (3-5 microM) was studied in taenia caeci smooth muscle cells. Membrane potential hyperpolarization was observed in intact muscle preparations and this response could be separated into two phases, depending on the state of a membrane-bound calcium compartment. The effect of alpha 1-adrenergic stimulation was also measured by [3H]inositol incorporation into phospholipid and inositol phosphate fractions of taenia cell suspensions both in the absence and presence of 2.5 mM extracellular calcium. In the absence of extracellular calcium the inositol phospholipids increased within 15 s after stimulation, followed by enhanced inositol phosphates. With calcium present there was a biphasic increase in the phosphatidylinositol 4,5-bisphosphate (PIP2) fraction with a simultaneous release of inositol phosphates. Lithium ions affected the incorporation of label into the lipids but not into the inositol phosphate fractions. These findings suggest that, in taenia caeci cells, alpha 1-adrenergic-induced membrane hyperpolarization resulting in muscle relaxation is associated with changes in the PIP2 content.

Adrenergic alpha-Agonists↗

PubMed1986

The effect of cisapride on smooth muscle cells of guinea-pig taenia caeci.

Cisapride (5 X 10(-7) M) caused depolarization, enhancement of spike activity, increase in muscle tone and potentiation of the contraction evoked by transmural stimulation of taenia caecum of the guinea-pig at 35 degrees C. At higher cisapride concentrations (2.5 X 10(-6) M) the potentiation of the evoked contraction was less pronounced or was even reversed into inhibition. Muscle tone was also enhanced by cisapride after relaxation of the smooth muscle cells by isobutylmethylxanthine (4 X 10(-5) M), a phosphodiesterase inhibitor. This effect of cisapride on muscle tone was smaller in the presence of atropine (10(-6) M), prazosin (10(-6) M) and propranolol (10(-6) M) and was also decreased in the presence of tetrodotoxin (3 X 10(-7) M). With these receptor blocking agents cisapride (5 X 10(-7) M) also depolarized smooth muscle cells and increased spike activity. The amplitude of the inhibitory junction potential represented by hyperpolarization was also enhanced and was followed by a more pronounced rebound activity. The depolarization induced by cisapride persisted in low sodium-low chloride and calcium-free solution, respectively. The cisapride depolarization was completely inhibited in the presence of orthovanadate (1 mM). It is concluded that cisapride inhibits calcium extrusion by a direct action on the smooth muscle cells of taenia caecum, leading to depolarization and enhancement of electrical and mechanical activity.

Animals↗

PubMed1986

The influence of alpha, beta-methylene ATP on alpha 1-receptor-operated channels in guinea-pig taenia caeci.

The influence of the ATP analog alpha, beta-methylene ATP on the action of adrenaline on alpha 1-receptors of smooth muscle cells of guinea-pig taenia caeci was studied by measuring potential changes. The preparation was superfused (1 ml/min) with Krebs solution or calcium-free solution containing atropine (10(-6) M) and propranolol (10(-6) M) at 22 degrees C, using the sucrose-gap method. The ATP analog (10(-5) to 4 X 10(-4) M) and adrenaline (10(-5) M) both caused a transient hyperpolarization in the absence of external calcium (20 min). The response (area under the 'curve') evoked under calcium-free conditions (20 min) increased with the concentration of the ATP analog. The response was diminished when preceded by the adrenaline response (10(-5) M) or when evoked after repeated addition of the analog to the superfusate (35 min). The adrenaline response was also diminished when preceded by the ATP analog. The responses to the ATP analog or adrenaline in the presence of apamin (3 X 10(-7) M) in the absence of external calcium were characterized by depolarization of the muscle cells. Repeated addition of the ATP analog or adrenaline to the preparation under these conditions did not cause any effect. The results suggest strongly that adrenaline and alpha, beta-methylene ATP both activate the same calcium-dependent process, producing calcium mobilization and the opening of apamin-sensitive potassium channels. Besides this action the ATP analog also activates apamin-sensitive potassium channels and this activation is independent of the availability of calcium in the adrenaline-sensitive pool.

Adenosine Triphosphate↗

PubMed1986

Neural control of gastro-intestinal motility; events following receptor activation.

The motility of the mammalian gastro-intestinal tract is regulated by a number of neuronal systems. The postganglionic, intramural parts of these systems are characterized by their neurotransmitters as cholinergic, adrenergic and 'purinergic' nerves, respectively. The transmitter acetylcholine evokes contractions of the smooth muscle cell, whereas both noradrenalin and the transmitter from the 'purinergic' nerves, presumably ATP, induce relaxations of smooth muscles. Agents and actions which influence the neurohumoral transmission and the mechanisms underlying the effects induced by the transmitters in smooth muscle cells are reviewed.

4-Aminopyridine↗

PubMed1985

Effector mechanisms for alpha,beta-methylene ATP and ATP derivatives in guinea-pig taenia caeci.

The effects of the ATP analog alpha, beta-methylene ATP and ATP derivatives on smooth muscle cells of guinea-pig taenia caeci were studied by measuring potential changes. The preparations were superfused (1 ml/min) with Krebs solution or calcium-free solution containing atropine (10(-6) M), prazosin (10(-6) M) and propanolol (10(-6) M) using the sucrose-gap method at 22 degrees C. The ATP analog (10(-5) M to 4 X 10(-4) M) caused slowly developing hyperpolarization in the presence of calcium. Hyperpolarization also occurred on addition of the analog in calcium-free medium. The area of the response increased with the analog concentration (10(-5) M to 4 X 10(-4) M). The response evoked after repeated addition of the ATP analog had slightly lower amplitude and slower onset than the first response both in the presence and the absence of calcium. The area of the response to the ATP analog in the absence of calcium was also decreased when preceded by the ATP response. When the opposite experimental sequence was used the ATP response was strongly inhibited, when preceded by the analog response evoked by the same concentration. The ATP analog caused depolarization of the muscle cells in the presence of apamin (3 X 10(-7) M), which was also observed with ATP. The ATP derivatives (4 X 10(-4) M) caused hyperpolarization of the smooth muscle cell membrane, except hypoxanthine and inosine which were inactive.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗

PubMed1985

Responses evoked by electrical stimulation, adenosine triphosphate, adenosine and 4-aminopyridine in taenia caeci of the guinea-pig.

Electrical stimulation of the guinea-pig taenia caeci (5 Hz, 2 s) caused enhancement of the [3H]purine flux from [3H]adenosine pools, accompanied by hyperpolarization (inhibitory junction potential) and relaxation of the muscle cells (35 degrees C). Interaction with receptors sensitive to catecholamines and acetylcholine was prevented by phentolamine (10(-6)M), propranolol (10(-6)M) and atropine (10(-6)M, respectively. The hyperpolarization and relaxation were completely inhibited by tetrodotoxin (TTX; 3 X 10(-7)M) but a substantial part of the [3H]purine flux persisted. The flux from the [3H]purine pool, from the [3H]methylcholine pool and from the noradrenaline pool was enhanced in the presence of 4-aminopyridine (3 X 10(-4)M; 4-AP), known to facilitate transmitter release. The release from the [3H]methylcholine pool was limited by hemicholinium (HC-3; 5 X 10(-4) M) and the release of noradrenaline was limited by reserpine (5 mg/kg; 24 h). The excess release of [3H]purine caused by 4-AP was completely abolished in the presence of TTX in preparations treated with HC-3 and reserpine. Addition of 4-AP to the Krebs solution evoked contraction of the smooth muscle cells. This response was abolished in the presence of HC-3 or atropine. The relaxation was also observed in reserpinized preparations in the presence of HC-3 and was not inhibited by either phentolamine or propranolol but was abolished in the presence of TTX. Hyperpolarization and suppression of spike activity accompanied the relaxation induced by 4-AP in reserpinized preparations treated with HC-3. Comparable responses were evoked by electrical stimulation of taenia caeci, by adenosine triphosphate (4 X 10(-4) M; ATP) and by adenosine (4 X 10(-4) M) in these experimental conditions. These responses evoked by electrical stimulation and by ATP were reversed in the presence of apamin (3 X 10(-7) M); the effect was reflected by an increased spike activity and contraction of the muscle cells in contrast to the adenosine response.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Aminopyridine↗

PubMed1984

The effect of forskolin on smooth muscle cells of guinea-pig taenia caeci.

Forskolin (0.5-10 microM) caused hyperpolarization and relaxation of the smooth muscle cells of guinea-pig taenia caeci (35 degrees C) as measured with the sucrose-gap method. Membrane conductance, reflected by the amplitude of the electrotonic potential, was not changed during the response. The hyperpolarization could also be evoked in the absence of extracellular calcium, calcium and potassium, or calcium and sodium. Further, the 45Ca2+ efflux from taenia caeci was enhanced by forskolin. The results support the concept that calcium extrusion across the plasma membrane is promoted in the presence of forskolin by stimulation of electrogenic calcium pumping.

Animals↗

PubMed1984

The contribution of calcium and potassium to the alpha-action of adrenaline on smooth muscle cells of the portal vein, pulmonary artery and taenia caeci of the guinea-pig.

The role of calcium and potassium in the alpha-action of adrenaline in pulmonary artery and portal vein was compared with that in taenia caeci by measuring changes in membrane potential, muscle contraction and ion fluxes in quiescent preparations from guinea-pigs (23 degrees C). The depolarization evoked by adrenaline (5 x 10(-8)-3 x 10(-5) M) was sustained in portal vein; in pulmonary artery it declined to a constant level after reaching an initial maximum. In calcium-free medium (20 min) containing EGTA (0.4 mM) and high magnesium (6.2 mM) adrenaline did not affect the membrane potential or the contractile state of the portal vein. Under these conditions the sustained phase of the response was abolished in the pulmonary artery; the remaining transient depolarization and contraction could be evoked only once. Adrenaline (3 x 10(-5) M) caused an increased 45Ca loss and 86Rb loss from the pulmonary artery and taenia caeci in calcium-free solution; a second addition of adrenaline to the calcium-free solution did not enhance the 45Ca loss from these tissues. The portal vein responded with an enhanced 86Rb loss on addition of the alpha-agonist. The bee toxin apamin (3 x 10(7) M) did not modify the depolarization, the contraction or the 45Ca and 86Rb fluxes evoked by adrenaline in the blood vessels. Enhancement of the 86Rb loss from taenia in the presence of adrenaline was prevented by apamin, but the excess loss of 45Ca was not abolished. It is concluded that adrenaline enhances cytoplasmic calcium by promoting calcium entry from the extracellular space in portal vein. In pulmonary artery and taenia caeci this is accompanied by mobilization of calcium from a cellular structure. Calcium entry facilitates triggering of the contractile proteins in vascular smooth muscle and is associated with membrane depolarization; in taenia caeci the mobilization of calcium caused by alpha-receptor activation is associated with the opening of potassium channels producing hyperpolarization and accordingly relaxation of the smooth muscle cells.

Animals↗

PubMed1983

The effect of some new aminopyridines on mammalian non-myelinated nerve fibres.

We evaluated the action of 2,4-, 3,4-diaminopyridine and 3-[(dimethylamino)carbonyl]amino,4-aminopyridine (LF-14) on non-myelinated fibres of the guinea-pig vagus nerve. The amplitude and duration of the compound action potential were enhanced similarly by all of the aminopyridines. The propagation velocity of the compound action potential and electrogenic sodium pumping were not changed by the aminopyridines. The results show that 2,4-diAP and LF-14 affect non-myelinated nerve fibres of the guinea-pig in the same way as does 3,4-diAP; sodium pumping was not modified by the aminopyridines.

4-Aminopyridine↗

PubMed1982

Calcium and the action of adrenaline, adenosine triphosphate and carbachol on guinea-pig taenia caeci.

1. The action of adrenaline (in the presence of propranolol; 3 x 10(-6) M), adenosine triphosphate (ATP) and carbachol on guinea-pig taenia caeci, and the interaction between these agonists, was studied by measuring changes in membrane potential using the sucrose-gap method in quiescent preparations at 22 degrees C.2. A sustained hyperpolarization was caused by addition of adrenaline (3 x 10(-6) M) and by applying adenosine triphosphate (ATP; 4 x 10(-4) M) for 5 min in Krebs solution. In calcium-free medium containing EGTA (0.4 mM) and high magnesium (6.2 mM), both the alpha-agonist and ATP caused a transient hyperpolarization which passed off within 5 min, although the agonist was still present.3. The transient hyperpolarization evoked by these agonists in the absence of calcium could be evoked only once. The response was restored after exposure to high calcium, (40 mM for 2 s, or 10 mM for 30 s). The maximum amplitudes of the hyperpolarization caused by adrenaline or ATP after exposure to high calcium (40 mM or 10 mM) were similar, while the maximum hyperpolarization after application of 2.5 mM-calcium was smaller.4. The area of the maximal response evoked by adrenaline or ATP was independent of the exposure time to calcium-free solution after removal of the extracellular calcium (20 min). The sum of the areas of a first submaximal response, obtained by applying adrenaline for less than 5 min to the calcium-free solution (20 min), and of the second response (5 min application) elicited after continuing in calcium-free medium for another 8 min, was constant.5. In the presence of the bee toxin apamin (10(-7) M), addition of ATP (4 x 10(-4) M) caused depolarization of the membrane both in the presence and absence of external calcium. These responses were not blocked in low sodium solution (22.7 mM) but were reduced by the calcium antagonist D600 (2 x 10(-5) M).6. In calcium-free conditions the alpha-response to adrenaline was decreased by a preceding addition of ATP and vice versa. Abolition of the ATP response (4 x 10(-4) M) by adrenaline (10(-5) M) was prevented by blocking the alpha-receptors with phentolamine (2 x 10(-5) M).7. Carbachol (5 x 10(-7)-5 x 10(-5) M) depolarized the muscle cells in calcium-free medium; a second addition of carbachol also caused depolarization, the amplitude being lower. The carbachol depolarization was dependent on the exposure time to calcium-free solution.8. The adrenaline response was reduced by about 25% by carbachol if applied previously, independent of the carbachol concentration (5 x 10(-7)-5 x 10(-5) M). The carbachol response, however, was not affected if preceded by the alpha-response.9. It is concluded that ATP and the alpha-agonist, after binding to their receptor sites, activate the same mechanism, which is mobilization of calcium from the same membrane compartment to open potassium channels, causing hyperpolarization of the muscle cell membrane; the hyperpolarization is transient or sustained in nature depending on the availability of external calcium to replenish the calcium compartment localized in the membrane. This adrenaline and ATP-sensitive calcium compartment is distinct from that which is sensitive to carbachol.

Adenosine Triphosphate↗

PubMed1981

Dual action of high energy adenine nucleotides in comparison with responses evoked by other adenine derivatives and intramural nerve stimulation on smooth muscle.

Fundic strips from stomach smooth muscle of the guinea-pig responded with a contraction preceded by a relatively small relaxation upon addition of the high energy adenine nucleotides ADP and ATP at 37 degree C. The contractile response was concentration-dependent in the range of 10(-8) - 10(-4) M, while the relaxation appeared at higher concentrations (10(-6) - 10(-4) M). The contractile phase observed in the presence of ADP or ATP was inhibited by the prostaglandin antagonist p-benzyl-4-(1-oxo-2-(4-chlorobenzyl)-3-phenylpropyl)phenyl phosphonate (N-0164; 5 X 10(-8) M) The low energy nucleotide AMP, adenosine and the ATP analogue beta, gamma-methyleneadenosine 5'-triphosphate caused relaxation of the stomach muscle. This relaxation was not affected by N-0164 (5 X 10(-8) M). Stimulation of the non-adrenergic inhibitory nerves caused relaxation of the muscle cells, in contrast to the effect of ATP. This seems to be in conflict with the purinergic nerve hypothesis. However, the relaxation evoked by field stimulation may have been due adenosine if it can be assumed that ATP is degraded after its possible release from nerve terminals. Furthermore, the limited availability of ATP if released from nerves for the short period of stimulation is presumably ineffective to stimulate prostaglandin biosynthesis. The results suggest that synthesis of prostaglandins is promoted by the high energy adenine nucleotides ADP and ATP which induce contraction of stomach smooth muscle in contrast with the low energy adenine derivatives and stimulation of the intramural non-adrenergic nerves which produce muscle relaxation.

Adenosine↗