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M Randic

Publications and source records attributed to M Randic.

28 records · Page 2Linked to original sources
PubMed1988

Actions of calcitonin gene-related peptide on rat spinal dorsal horn neurons.

The membrane actions of calcitonin gene-related peptide (CGRP) and the effect on the Ca-dependent action potential of dorsal horn neurons have been investigated by means of an intracellular recording technique in the immature rat in vitro spinal cord slice-dorsal root ganglion preparation. Bath application of CGRP (10(-8)-10(-6) M for 1-10 min) produced a slow reversible depolarization in about one-third of the cells examined. Biphasic membrane response consisting of an initial hyperpolarization followed by a late prolonged depolarization was seen in a smaller proportion of tested cells. Both membrane responses were present, and even enhanced, when synaptic transmission and Na spikes were blocked by perfusing the slice with a TTX-containing Krebs solution. The CGRP-induced membrane changes were also present in media containing TTX and TEA. The CGRP-evoked depolarization was associated with an increase in the input resistance, and enhanced excitability in a majority of neurons tested. In addition, CGRP modified the duration of Ca-dependent action potentials of dorsal horn neurons, the most consistent change being a prolonged increase in the spike duration. Our results are consistent with a neurotransmitter or neuromodulator role for CGRP in the rat spinal dorsal horn.

Action Potentials↗
PubMed1988

Actions of calcitonin gene-related peptide on rat sensory ganglion neurones.

The membrane actions of calcitonin gene-related peptide (CGRP) and the effect of CGRP on the Ca-dependent action potential of rat dorsal root ganglion (DRG) neurons have been studied by means of an intracellular recording technique in isolated DRG of 2-3-week-old rats in vitro. Bath application of CGRP (10(-8)-10(-6) M for 1-5 min) elicited a slow reversible hyperpolarization and this hyperpolarizing effect was still observed in the medium containing TTX and TEA. However, about half of the large cells, classified by duration of action potential, were depolarized by CGRP. These membrane effects of CGRP were associated with an increase in membrane input resistance (about 20%). In addition, CGRP increased the duration of Ca-dependent action potentials. Our results are consistent with the role of CGRP as an excitatory neurotransmitter or neuromodulator in DRG-spinal cord.

Animals↗
PubMed1982

Vasoactive intestinal polypeptide excites mammalian dorsal horn neurons both in vivo and in vitro.

Vasoactive intestinal polypeptide (VIP) applied by iontophoresis and/or pressure microinjection causes a strong excitation of more than 75% of all tested spinal neurons in laminae I-VII of both the cat intact spinal cord and the rat spinal cord slice preparation. In the cat intact spinal cord the excitation is not limited to a single population of neurons but is observed in all categories of units recognized in spinal preparations of cats in this area on the basis of their excitability by different kinds of cutaneous afferent input. In the rat spinal cord slice preparation, VIP depolarized dorsal horn neurons and increased their excitability. The depolarization was associated with a decrease in neuronal input resistance. These results are consistent with the possibility that VIP may have a physiological role in synaptic function, either as a transmitter or as a modulator.

Animals↗
PubMed1975

Molecular connectivity. I: Relationship to nonspecific local anesthesia.

A very significant linear correlation was found between a recently proposed connectivity index and molecular polarizability, cavity surface areas calculated for water solubility of alcohols and hydrocarbons, and biological potencies of nonspecific local anesthetics. The simplicity of calculation of the index from the connectivity in the molecular skeleton, together with the very significant correlation, indicates its practical value.

Anesthetics, Local↗
PubMedDate not supplied

Effects of substance P analogues on spinal dorsal horn neurons.

The effects of iontophoretically applied (D-Pro2, D-Phe7, D-Trp9)-SP and (D-Pro2, D-Trp7,9)-SP on the spontaneous and evoked activity of functionally identified cat spinal dorsal horn neurons have been investigated in vivo by means of extracellular single unit recording technique. In addition, the rat spinal cord slice preparation has been used to study the actions of (D-Pro2, D-Trp7,9)-SP and (D-Arg1, D-Pro2, D-Trp7,9, Leu11)-SP on the resting membrane potential of dorsal horn neurons and also on their responses to dorsal root stimulation and exogenous SP application. We have observed that both (D-Pro2, D-Phe7, D-Trp9)-SP and (D-Pro2, D-Trp7,9)-SP produced an excitation of about 15% of all neurons tested and had a weak antagonistic effect against SP in the cat spinal cord. (D-Pro2, D-Trp7,9)-SP suppressed the SP-induced excitation in 63% of examined cells. In addition, depression of the glutamate-induced excitation and spontaneous activity was evident in 10% and 19% of the cat dorsal horn neurons tested, respectively. In the spinal cord slice preparation (D-Arg1, D-Pro2, D-Trp7,9, Leu11)-SP proved to be a more potent antagonist of the SP-induced depolarization and the dorsal root-elicited slow depolarization, if compared with (D-Pro2, D-Trp7,9)-SP.

Animals↗
PubMedDate not supplied

Quantitative structure-activity relationship of flavonoid analogues. 3. Inhibition of p56lck protein tyrosine kinase.

Quantitative structure-activity relationship (QSAR) studies on 104 flavonoid derivatives as p56lck protein tyrosine kinase (PTK) inhibitors were performed, using a large number of molecular descriptors calculated by CODESSA software. Multiple linear regression and orthogonalization of descriptors were applied to generate models for the prediction of biological activities for binding flavonoids to PTK. The obtained results demonstrate in detail the importance of electrostatic and quantum chemical descriptors for the interaction of flavonoids with the specific p56lck enzymatic active site environment. In particular, the maximal total interaction for a C-O bond is the most important factor in regression. Use of orthogonalization in regression models provides a valuable improvement for the interpretative and predictive capacity of structure-activity relationships found.

Enzyme Inhibitors↗
PubMedDate not supplied

On structural interpretation of several distance related topological indices.

We consider the role that individual bonds play in bond-additivities in order to better understand the structural basis of various topological indices. In particular we consider indices closely related to the Wiener index (W) and the distance matrix and search for optimal weights of terminal and interior CC bonds in alkanes for a selection of physicochemical properties. It is interesting to note that different properties are associated with different relative roles of the exterior and the interior CC bonds.

Journal Article↗