Evans, Anthony Mark

2018-01-31T11:43:17Z

2018-01-31T11:43:17Z

1990

A study has been made of the secretory response and the electrical response (a hyperpolarization followed by a depolarization) mediated by dopamine receptors of the cockroach (Nauphoeta cinerea Olivier) salivary gland in-vitro. RECEPTOR CLASSIFICATION: The selective D1 agonists fenoldopam and SK38393, and the selective D2 agonists LY163502 and quinpirole induced, in descending order of potency, secretion and a concomitant electrical response from the acinar cells. The secretory and electrical responses to dopamine were found to be antagonised by, in descending order of potency, chlorpromazine (a non - selective dopamine antagonist), SCH23390 (a selective D1 antagonist), haloperidol and metaclopramide (selective D2 antagonists). Another D2 antagonist (p)sulpiride and the highly selective D2 antagonist domperidone did not inhibit either the secretory or electrical responses. These results taken together suggest that the receptor mediating the secretory and electrical response are the same, and analogous to the mammalian D1 sub -type. This suggestion is strengthened by the fact that SCH23390 inhibited the secretory and electrical response to all the selective agonists, while (p)sulpiride did not. Although domperidone did response to dopamine, three other actions were observed: one, post- synaptic, led to the potentiation of the hyperpolarization; this action was shared by (p)sulpiride. A separate post- synaptic action resulted in the inhibition of the depolarizing phase of the response. Finally a presynaptic action led to the abolition of the response to nerve stimulation. EFFECTS OF THE CALMODULIN ANTAGONISTS W7 AND CALMIDAZOLIUM: In an attempt to investigate the role of calmodulin in stimulus - secretion coupling within the salivary gland, the actions of two calmodulin antagonists, W7 and calmidazolium, were studied. In high concentrations, but within the range in which they are known to inhibit calmodulin, W7 and calmidazolium were found to inhibit dopamine- induced secretion and hyperpolarize the acinar cells. The hyperpolarization was not inhibited by SCH23390, and resulted from an increase in cytosolic free calcium, released from the same source as that accessed by dopamine. Lower concentrations of these two antagonists caused submaximal secretion and potentiated dopamine - induced hyperpolarizations. An interpretation of these results is that calmodulin promotes secretion, and exerts a negative control on cytosolic free calcium by an independent process which can be selectively inhibited.

http://hdl.handle.net/1842/27986

The University of Edinburgh

Annexe Thesis Digitisation Project 2017 Block 16

Already catalogued

Dopamine receptors of the cockroach salivary gland

The dopamine receptors of the cockroach salivary gland

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Doctoral

PhD Doctor of Philosophy