The pharmacology of calcitonin

McArdle, CA, 1984. The pharmacology of calcitonin. PhD, Nottingham Trent University.

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Abstract

The mechanisms underlying the pharmacological effects of calcitonin (CT) have been investigated. The haemodynamic and antinociceptive effects of CT have been adopted as models for study as both are readily quantified, appear to involve modulation of neuronal activity and are of potential therapeutic use.

The antinociceptive effect of centrally administered CT in mice was found to be attenuated by pretreatment with p-chloropheny1alanine (but not by methysergide or a-methy1-p-tyrosine) and central administration of 5-hydroxytryptamine with CT overcame the effect of p- chlorophenylalanine. These observations form the basis of a model in which CT antinociception is attributed to modulation of the activity of central tryptaminergic neurones. However, CT did not alter the concentration of 5"hydroxytryptamine (or its major metabolite 5"hydroxyindole- acetic acid) in the mouse or rat brain. The hormone may therefore produce localised alterations in 5"hydroxytryptamine concentration or turnover.

As recent reports indicate that the CT gene is transcribed to produce calcitonin gene-related peptide (CGRP) rather than CT in neural tissue, the possible antinociceptive effects of salmon-CT, human- CT and CGRP have been compared. All three peptides produced antinociception but the effects of human-CT and CGRP were more transient and required higher doses. The possibility of action of CT on putative central CGRP receptors is discussed.

Salmon-CT i.v. has been found to produce a pressor response in rats made hypotensive by haemorrhage, but is without effect in normo- tensive rats or those made hypotensive by Pithing. The pressor effect was greatly attenuated by chemical sympathectomy suggesting that the hormone potentiates sympathetic outflow. Centrally administered salmon-CT produced a pressor response in both normotensive and haemorrhaged rats, the latter effect was not greatly attenuated by chemical sympathectomy. It is concluded that the site and mechanism of action of centrally and peripherally administered salmon-CT differ in these models.

With regard to the cellular mechanism of action, CT was found to inhibit depolarisation stimulated uptake of by slices of rat midbrain, to increase the cyclic adenosine 3', 5'-monophosphate content of mouse hypothalamus in vivo, and to stimulate adenylate cyclase activity in homogenates of mouse hypothalamus. These effects could clearly reflect effects of CT on cellular metabolism thus producing the altered neuronal activity assumed to underlie the antinociceptive and haemodynamic effects of the hormone.

Item Type:	Thesis
Creators:	McArdle, C.A.
Date:	1984
ISBN:	9781369325720
Identifiers:	Number Type PQ10290323 Other
Divisions:	Schools > School of Science and Technology
Record created by:	Laura Ward
Date Added:	08 Jul 2021 08:53
Last Modified:	22 May 2024 14:16
URI:	https://irep.ntu.ac.uk/id/eprint/43369

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