Quantitative pharmacological studies on small neurones

Yavari, Parviz (1979) Quantitative pharmacological studies on small neurones. University of Southampton, Doctoral Thesis.

Abstract

Seven identified and a number of unidentified neurones in the suboeoophageal ganglia of the snail, Helix aspersa were studied by intracellular microelectrode recording techniques. These neurones responded to iontopharetio or bath application of a number of neurotransmitter substances ouch as acetylcholine (ACh), depamino, glutamate and uerotonin (5-HT) by depolarization-excitation (designated as D cells) or by hyperpolarization-inhibition (designated as H cells). Doseresponse curves were constructed for the transmitters in these cells and from these the pD2 values of transmitters (a measure of affinity of transmitters to the receptors in the tissue) were determined. Comparison of pDD values within each group of ACh-sensitive cells showed that the affinity of silent cells to ACh was greater than that of the active cells showing action potentials. Seven cholinergic antagonists were studied on the D and H responses of ACh to determine their potency and nature of blockade of these responses. Dose-response curves of ACh were determined in the presence of various concentrations of these antagonists and it was shown that some antagonists produced competitive and some non-competitive antagonisms of the ACh responses. For the competitive antagonists pA2 values (a measure of affinity and potency of these antagonists) were determined. The antagonists had different orders of potency in antagonizing the D and the H responses of ACh. The order of potency of antagonists on the ACh H response (C1--mediated response) showed that the ACh receptors mediating this response were similar to the nicotinic receptors found in the mammalian neuromuscular junctions while the order of potency of antagonists on the ACh D response suggested that the receptors mediating this response were similar to the nicotinic receptors of the mammalian autonomic ganglia.The antagonist d-tubocurarine was screened for its antagonistic activity on the D and H responses of 5-HT, dopamine and glutamate in six identified cells in this preparation. d-Tubocurarine up to 10-314 had no effec on the fast H responses of glutamate and dopamine while at l0-`SM - 10 reversibly and dose-gradedly potentiated the slow H responses of dopamine; potentiation was both gn the amplitude and the duration of the response. d-Tubocurarine l0-4 - 10-3M antagonized the fast D responses of 5-HT, dopamine and glutamate on these cells. The rate of recovery of responses from d-tubocurarine antagonism was studied and it was shown that 5-HT, dopamine and glutamate D responses took longer to recover from the d-tubocurarine antagonism than did the ACh response in the first exposure to the antagonist. After repeated exposures to d-tubocurarine the ACh D response was fully reversible while the D response to 5-HT, dopamine and glutamate responses were semi-reversible. Experiments were carried out on cell Fl (in visceral ganglion) by application of mixtures of ACh and 5 -ET (cell was D to both transmitters) to study receptor-ionophore relationships of these transmitters. Results of these studies suggested that ACh and 5-HT used separate ionophores in this cell. Studies with d-tubocurarinne were discussed in terms of mechanisms of specific and non-specific actions of this antagonist in Helix aspersa neurones.

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