Further evidence on the interaction of muramyl dipeptide with the serotonergic system.

The mode of interaction between muramyl dipeptide (MDP), a compound with immunopharmacological activities, and 5-hydroxtryptamine (5-HT, serotonin) was studied in isolated nerve-smooth muscle preparations of the carp stomach. Application of exogenous 5-HT evoked direct smooth muscle contractions; electric neurogenic stimulation evoked twitches due to release of 5-HT from nerve endings. Contractions evoked by a high concentration of 5-HT (3-30 microM) were resistant to atropine and potentiated in the presence of MDP.

The effect of immunomodulator muramyl dipeptide on serotoninergic responses of isolated neuromuscular preparations.

The mode of action of muramyl dipeptide (MDP), a compound with immunopharmacological properties, was studied in isolated nerve smooth muscle preparations with different receptor systems. The amplitudes of contractions evoked directly by stimulants as well as neurogenic twitches or relaxations were registered. In the rat stomach strip EC50 of acetylcholine, serotonin (5-HT) and KCl was estimated.

The topographical basis and frequency-dependence in the effect of different compounds on neurogenic contractions of the guinea-pig ileum.

The site of action of compounds affecting either Na+/K+ or Ca2+ conductances in nerve terminals was studied in myenteric plexus-longitudinal muscle strips from the guinea-pig ileum. A preparation in a special triple bath was drawn through two rubber membranes, dividing a strip into three segments. Neurogenic stimulation of the oral segment, set up nerve action potentials in the neurons projecting axons up to the aboral segment.

An attempt to localize the site of action of different agents within cholinergic motor neurones of the myenteric plexus-longitudinal muscle preparation of the guinea pig ileum by the triple bath method.

The site of action of cholinergic, adrenergic, peptidergic and opioid agents was studied in myenteric plexus-longitudinal muscle strips from the guinea pig ileum. A preparation in a special triple bath was drawn through two rubber membranes, dividing the strip into three segments. Neurogenic stimulation of the oral segment, set up nerve action potentials also in the neurones projecting axons up to the aboral segment.

Non-synaptic cholinergic modulation of neurogenic twitches of the guinea-pig ileum.

The effect of cholinergic and anticholinergic compounds on conduction of neuronal excitation has been studied in myenteric plexus-longitudinal muscle strips from the guinea-pig ileum. A preparation in a special triple bath was drawn through two rubber membranes dividing the strip into three segments. Neurogenic stimulation of the oral segment set up nerve action potentials propagating aborally across the middle segment (10 mm) so that the aboral segment might be also invaded, eventually.

[Characteristics of the aged surgery patient].

In 32 old people selected at random (16 men and 16 women) indicators of the water and mineral salt balance were investigated as well as renal and hepatic functions, nutritional status, serum insulin, thyroxine and triiodothyronine and in 12 also changes after operation. The findings indicate that it is necessary to ensure clinical and biochemical monitoring as well as proper preparation of old people for a planned surgical operation. Old people must be always considered critical patients and it is important to provide extra preoperative and postoperative care.

Non-junctional modulation of neurogenic twitches of the guinea-pig ileum by some peptides and other compounds in the triple bath.

The effects of some neuropeptide transmitter candidates and of some other neurotoxins or drugs on conduction of neural excitation were studied in myenteric plexus-longitudinal muscle strips from the guinea-pig ileum. A preparation in a special triple bath was drawn through two rubber membranes dividing the strip into three segments. Neurogenic stimulation of the oral segment set up nerve action potentials propagating aborally across the middle segment so that the aboral segment might also be invaded.

[Nitric oxide--a new and nontraditional transmitter].

NO is obviously identical with the relaxation factor produced by the vascular endothelium (EDRF) and is also the substance responsible for some other biological activities. It is formed in the organism from L-arginine by the action of the enzyme NO synthetase. The main mechanism of action is the activation of the enzyme guanyl cyclase and the result is an increase of the intracellular level of cyclic guanyl monophosphate.

[A rational diagnostic program for hypertension in children].

Early screening of subjects liable to develop cardiovascular diseases is one of the main tasks of preventive cardiology of child age. The authors present a rational programme for the screening and diagnostic of hypertension in children, its aim being to differentiate primary and the most frequent secondary forms of hypertension; this will create prerequisites for its adequate treatment (non-pharmacological and pharmacological) as well as for dispensarization. Review.

The topographical basis of cholinergic transmission in guinea-pig ileum myenteric plexus.

Myenteric plexus-longitudinal muscle strips were used to study nerve action potential propagation and transmission and their differences between the proximal and the distal regions of cholinergic terminals. Neurogenic twitches of a portion of the strip were evoked by focal electrical stimulation. Twitches mediated by the distal regions of cholinergic nerve terminals were more influenced by drugs affecting Ca2+ "utilization" (Bay K 8644, kappa opiate ligand ethylketocyclazocine, changes in extracellular Ca2+ or Co2+ concentration) in contrast to twitches mediated by proximal regions of these terminals which were more influenced by drugs affecting sodium-potassium spike (tetrodotoxin, dendrotoxin, 4-aminopyridine, tetraethylammonium).

The effect of substance P on nerve action potential propagation and cholinergic transmission in the myenteric plexus of the guinea-pig ileum.

The effect of substance P on nerve terminals in myenteric plexus of the guinea-pig ileum was investigated. Neurogenic twitches of the myenteric plexus longitudinal muscle strip were recorded. Twitches of the strip portion where excitation involved the most distal parts of cholinergic nerve terminals were more increased by local application of substance P (0.

Interactions of neurogenic responses of longitudinal and circular muscle in the guinea-pig ileum.

The relationship between neurogenic responses of longitudinal and circular muscle was studied by measuring contractions and EMG or nonadrenergic, non-cholinergic (NANC) relaxations and NANC inhibitory junction potentials in different preparations of the guinea-pig ileum. NANC relaxation of longitudinal muscle was observed also without any preceding or concomitant circular muscle contraction ruling out the possibility that the latter might be the cause of the NANC relaxation. Circular muscle twitches or powerful contractions were absent if there was no preceding neurogenic or myogenic excitation of longitudinal muscle; in preparations with myenteric plexus-longitudinal muscle layers removed only small residual responses were seen although still under neurogenic influences.

The topography of cholinergic transmission in the mechanism of drug action at muscarinic synapses of the guinea-pig ileum.

The pharmacology of cholinergic neurogenic responses evoked by the participation of only the endings of axon terminals was compared to that of responses evoked by participation of the more proximal parts of the terminals also. Myenteric plexus-longitudinal muscle strips of the guinea-pig ileum were drawn through narrow orifices in 2 rubber membranes dividing a bath into 3 separate compartments. Oral segments were stimulated electrically by single impulses or by trains and local neurogenic contractions were evoked.

[Influence of prostaglandin synthesis blockade on the immunosuppressive effect of serotonin and haloperidol].

Administration of indomethacin (1.5 and 10 mg/kg) to CBA mice was found to produce a considerable increase of the number of plaque- and rosette-forming cells irrespective of the dose and the interval between its injection and immunization of the mice with ram erythrocytes (5 X 10(6)). The immunogenesis stimulation preserved in the mice after a lesion of the pituitary peduncle.

The topography and dynamics of cholinergic transmission in the myenteric plexus-smooth muscle preparation of the guinea-pig ileum; the effect of ketocyclazocine, a kappa opiate ligand.

Output of acetylcholine (ACh), neurogenic electromyogram (NEMG) and contractions of guinea-pig ileum preparations were studied during stimulation by high-frequency trains of impulses. Under control conditions the output of ACh per impulse after 2nd to 4th impulses during train stimulation (30 Hz) was higher by 20-40% than the level of ACh output during the first impulse. In the presence of ketocyclazocine (KTZ, 80 nmol x l-1) the output of ACh evoked by the first impulse was more effectively inhibited than that after impulses 2 to 4 so that the increase was higher (80-170%).

Role of substance P in post-tetanic potentiation in myenteric plexus-longitudinal muscle preparations; the effect of substance P-antagonist.

A role of substance P in post-tetanic potentiation in the myenteric plexus-longitudinal muscle preparation of the guinea-pig ileum was investigated by means of substance P-antagonist, (D-Pro2, D-Trp7,9)-substance P. After the addition of substance P-antagonist (10(-7)-10(-5) mol x l-1) a dose-dependent reduction of post-tetanic potentiation of neurogenic twitches was observed. Post-tetanic potentiation was actually abolished in the presence of 10(-5) mol x l-1 substance P-antagonist.

The influence of immune status on the in vitro sensitivity of serotoninergic receptors in the rat stomach strip.

Serotoninergic contractions of the rat stomach strip were evoked and EC50 determined. In preparations from control animals MDP, 50 mumol/l, decreased EC50 or sensitized the preparation. In the strips from animals where adjuvant arthritis was induced, higher sensitivity to 5-HT was observed and the sensitizing effect of MDP was retained.

Interactions between the duration of stimulation and noradrenaline on cholinergic transmission in the myenteric plexus-smooth muscle preparation.

Output of acetylcholine (ACh), electromyogram (EMG) recordings and contractions of myenteric plexus-longitudinal muscle strip preparations from the guinea-pig ileum were studied during stimulation by single impulses or by trains (30 Hz; 2 to 128 impulses) under control conditions and in the presence of noradrenaline (NA). During supramaximal stimulation NA (2.5 microM) inhibited both contractions of the smooth muscle and the release of ACh evoked by single impulses more effectively than those evoked by train stimulation so that in a train of 4 impulses the output of ACh per impulse after the 2nd to 4th impulses was 69 to 104% higher than the output after the 1st impulse.

How far from the stimulation site in myenteric plexus-longitudinal muscle preparations the neurogenic cholinergic contraction can be evoked?

Neurogenic contractions of a segment of myenteric plexus-longitudinal muscle strip preparations from the guinea-pig ileum were evoked. The site of electric stimulation was separated from the contracting segment by a gap preventing the spread of muscle action potentials set up in other regions. The width of the separating gap (2-20 mm) indicated the length of nerve fibers that could conduct impulses across and trigger cholinergic contractions behind the gap; it was more than 12 and less than 16 mm.

Post-tetanic potentiation at the nerve-muscle junction in the longitudinal muscle of the guinea-pig ileum. Possible role of substance P.

The effect of short tetanic stimulation (30 Hz for 25 s) on the following twitch responses of the myenteric plexus-longitudinal muscle preparation of guinea-pig ileum to electric stimulation (0.1 Hz) was investigated in the presence of naloxone and indomethacin. Post-tetanic potentiation (PTP) of the twitches observed in control experiments was abolished in preparations desensitized by substance P but it was not affected in preparations desensitized by serotonin or pretreated with methysergide.

The topography of posttetanic potentiation in guinea-pig ileum.

The myenteric plexus-longitudinal muscle preparation of the guinea-pig ileum offers, by its anatomical arrangement, the possibility of studying a new aspect of posttetanic potentiation (PTP); its topography. Evidence was sought and obtained that during PTP more distal junctional sites of cholinergic nerve terminals may be recruited into the transmitter secretion process.

An interaction of endogenous and exogenous opiates in the guinea-pig isolated ileum.

In the myenteric plexus-longitudinal muscle preparation of the guinea-pig ileum an interaction of exogenously applied opiates with posttetanic inhibition was studied. The electric tetanic stimulation (30 Hz) evoking the release of endogenous opioids resulted in an inhibition of neurogenic cholinergic twitch contractions (0.1 Hz) of the same preparation.

Smooth muscle stimulation by an immunomodulatory compound muramyl dipeptide: does it involve serotoninergic system?

Contractions evoked by muramyl dipeptide (MDP), a synthetic compound possessing immunostimulatory properties, were studied in several isolated nerve-smooth muscle preparations. The contractions by micromolar concentrations of MDP were evoked either by direct interaction with smooth muscle (rat stomach strip) or at least partly indirectly via neurogenic stimulation (guinea pig ileum); the effect was stereospecific since the MDP-D was not active. The insensitivity of the preparations to serotonin (5-HT), either inherent (vas deferens) or after 5-HT antagonists or after desensitization to 5-HT, prevented or markedly reduced the contractile activity by MDP.