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Biomedical subjects

M Luján

Publications and source records attributed to M Luján.

At least 37 records · Page 2Linked to original sources

Electrocardiographic alterations induced by repeated electrical stimulation of the heart at low intensity.

Repeated, low-intensity electrical stimulation of the heart gradually leads to the development of electrocardiographic abnormalities that culminate in cardiac arrhythmias, mainly A-V block in the isolated heart frog and ventricular and supraventricular tachyarrhythmias in the canine heart in situ. The pattern of development of these alterations shows some characteristics similar to the kindling phenomenon. Blockade of adrenergic influences on the heart offered complete protection against the development of cardiac arrhythmias. These results support the idea that a kindling-like effect can be induced by the periodic electrical stimulation of structures other than the CNS.

Animals↗

Kindling-like convulsive activities in the isolated ileum of the guinea pig. I. Electrical stimulation.

A kindling-like convulsive activity model produced by subthreshold, iterative electrical stimulation of the isolated male guinea pig ileum is described. In this model, the mechanical activity of the longitudinal muscular fibers of the ileum was systematically quantified in terms of the basic frequency, tonus, amplitude, and transient amplitude increments (A, n spikes/20 min) of "normal" contractions and presence of high-amplitude, paroxysmal, "epileptiform" contractures (B, n spikes/20 min). Changes in these parameters were statistically compared through consecutive stages of the same stimulated male ileum (I = initial activation, II = initial inhibition. IIIA = late activation, and IV = late inhibition) and equivalent stages of stimulated female and nonstimulated male ilea where "kindling-like" activities were only occasionally observed. Basic tonus, amplitude, and number of A spikes showed significant changes through consecutive stimulated male ileum "kindling" stages: increased from baseline to stage I, decreased from I to II, increased from II to III and from III to IIIA, and decreased from IIIA to IV. The number of B spikes significantly increased from II to III, III to IIIA, and IIIA to IV. No significant changes in baseline frequency were found through all stages nor in tonus, amplitude, A and B spikes between stage IV and the self-sustained activity observed 120 min after stimulation. In addition, there were significant correlations between B spikes vs. basic tonus and amplitude and A spikes when the stimulated male ileum shifted from stage II to IIIA (positive correlations) and from IIIA to IV (negative correlations). Basic tonus during stage I, basic amplitude during IIIA, A spikes during self-sustained activity and B spikes during III, IIIA, IV, and self-sustained activity were in the stimulated male ileum larger than those in both the stimulated female and the nonstimulated male ilea. Tonus and A spikes during III and IIIA in the stimulated male ileum were larger than in the nonstimulated, whereas tonus during IV and self-sustaining activity and amplitude during II in the stimulated male ileum were smaller than in the female stimulated ileum.

Animals↗

Kindling-like phenomenon in the isolated ileum of the guinea-pig.

Repeated bursts of low voltage electrical stimulation of the isolated ileum of the guinea-pig gradually leads to the development and progressive intensification of the tissue basal activity, culminating in spontaneous, sudden strong contractions of the preparation, which persist for several hours after the stimulation has been discontinued. The magnitude of these alterations are determined by the parameters of the stimulation, mainly by the number of electrical stimulations, the frequency of stimulation, and the interstimulus interval. Maximal alterations are obtained with periods of stimulation of 20 Hz for 10 sec, pulses of 3.0 msec, repeated every 20 min for 15 times. Phenytoin, flunitrazepam, diazepam, phenobarbital and carbamazepine effectively inhibited the fully developed phenomenon in the tissues. The effect described in this report may be related to kindling in the brain.

Animals↗

Pertussis toxin blocks the action of morphine, norepinephrine and clonidine on isolated guinea-pig ileum.

Administration of pertussis toxin (60 micrograms/kg i.p.) to guinea-pigs blocked the ability of morphine, norepinephrine and clonidine to inhibit electrically stimulated contractions in the isolated ileum. The toxin reached its maximum effect 6 days after its administration. The effect of the toxin was reversible; a slow but full recovery of the response to morphine was observed in ilea from guinea-pigs treated with toxin 18 days before the experiment. It is suggested, based on the known action of pertussis toxin, that inhibition of adenylate cyclase through Ni (guanine-nucleotide regulatory protein) is involved in the acute action of morphine, norepinephrine and clonidine in the motoneurons of the myenteric plexus of the ileum.

Adenylate Cyclase Toxin↗

Pharmacological characterization of opiate physical dependence in the isolated ileum of the guinea-pig.

1 Physical dependence was produced in ilea from naive guinea-pigs by exposure of the tissue to different opiates for logarithmically-spaced periods of time (20-320 min). The responsiveness of the tissue to naloxone, as indicated by a strong contracture of the ileum, was enhanced in contrast to that found in intestines not exposed to opiates. 2 The dose-response curves to naloxone obtained in tissues individually exposed to different opiates showed that their relative potency in increasing sensitivity to naloxone was as follows: levorphan greater than morphine greater than Met-enkephalin greater than nalorphine greater than pentazocine. 3 The naloxone-induced response was dose-dependent and was directly related to the opiate concentration and length of exposure. 4 Dextrorphan the inactive isomer of levorphan, did not increase the responsiveness of the tissues to the narcotic antagonist, indicating that the phenomenon is stereospecific. 5 The naloxone-induced contraction in ilea exposed for 320 min to morphine (1 x 10(-6)M) was not prevented or suppressed by the administration of a large dose of morphine (1 x 10(-5)M) before or immediately after the naloxone challenge. 6 The evidence presented here shows that a phenomenon resembling in vivo opiate physical dependence can be acutely produced in vitro with pharmacological characteristics similar to other naloxone-induced abstinence effects.

Animals↗

Morphine-theophylline interaction: antagonism or facilitation?

1 Morphine-theophylline interactions were investigated in both acute and narcotic-dependent preparations, in vitro and in vivo, using four different experimental models: LD50 doses of morphine and naloxone in the mouse; naloxone-induced contractions in the electrically-stimulated and opiate-dependent isolated ileum of the guinea-pig; naloxone-induced jumps in the mouse; an calcium uptake in synaptosomal preparations. 2 The LD50 of morphine was significantly increased by theophylline. 3 The lethal effect of theophylline was potentiated by pretreatment of the animals with naloxone. 4 Theophylline displayed protective effects in the inhibitory response to morphine and antagonism to the withdrawal response induced by naloxone in the electrically-stimulated isolated ileum of the guinea-pig. 5 The number of jumps induced by naloxone in morphine-dependent mice was significantly diminished by theophylline. 6 The inhibitory effect of morphine on the synaptosomal uptake of calcium was decreased by theophylline. 7 The effects of both morphine and theophylline on the cyclic nucleotides and the possible role of calcium in these actions are discussed.

Animals↗

Structure-activity relationships of enkephalins in the stimulated guinea pig ileum.

A number of analogs and homologs of methionine-enkephalin (H.Tyr. Gly.Gly.Phe.Met.OH) have been synthesized by the Merrifield method of solid phase peptide synthesis. Each peptide was assayed by inhibition of electrically evoked contraction of the guinea pig ileum. The minimum sequence required for biological activity in this preparation was found to be the pentapeptide unit. Methionine was readily replaced by norleucine to give an analog with approximately 50% of the potency of the parent compound. Leucineenkephalin has about 15-20% of the potency of the methionine dervative. Modification of the N-terminal tyrosine moiety (i.e. substitution by phenylalanine or removal of the amino group) practically abolished activity. Incorporation of O-methyl tyrosine into the peptide reduced potency to 1% of the parent compound. The significance of these and other findings in terms of the topography of the guinea pig ileum receptor site is discussed.

Animals↗