Effects of Some Antidepressant Drugs on Tryptaminergic Responses of the Rat Jejunum

Liu, Haihuang; Coupar, Ian M.; Irving, Helen Ruth

doi:10.1159/000072361

Cited by 3 publications

(2 citation statements)

References 24 publications

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“…These applications are well-founded given the widespread distribution of the 5–HT 7 receptor in the CNS and accumulating evidence for its functional effects. This includes the findings that some antidepressants, such as amitriptyline, have relatively high affinities at the 5–HT 7 receptor (see [ 48 , 50 , 73 ] for reviews) . The 5–HT 7 receptor was originally discovered in the CNS where particularly high expression was found in the thalamus and hypothalamus.…”

Section: Clinical Relevancementioning

confidence: 99%

Human 5-HT4 and 5-HT7 Receptor Splice Variants: Are they Important?

Coupar¹,

Desmond²,

Irving

2007

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G-protein-coupled receptors (GPCRs), which are encoded by >300 genes in the human genome, are by far the largest class of targets for modern drugs. These macromolecules display inherent adaptability of function, which is partly due to the production of different forms of the receptor protein. These are commonly called 'isoforms' or 'splice variants' denoting the molecular process of their production/assembly. Not all GPCRs are expressed as splice variants, but certain subclasses of 5-HT receptors are for example, the 5-HT4 and 5-HT7 receptors. There are at least 11 human 5-HT4 and three h5-HT7 receptor splice variants. This review describes their discoveries, nomenclature and structures. The discovery that particular splice variants are tissue specific (or prominent) has highlighted their potential as future drug targets. In particular, this review examines the functional relevance of different 5-HT4 and 5-HT7 receptor splice variants. Examples are given to illustrate that splice variants have differential modulatory influences on signalling processes. Differences in agonist potency and efficacies and also differences in desensitisation rates to 5-HT occur with both 5-HT4 and 5-HT7 receptor splice variants. The known and candidate signalling systems that allow for splice variant specific responses include GPCR interacting proteins (GIPs) and GPCR receptor kinases (GRKs) which are examined. Finally, the relevance of 5-HT receptor splice variants to clinical medicine and to the pharmaceutical industry is discussed.

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Section: Clinical Relevancementioning

confidence: 99%

Human 5-HT4 and 5-HT7 Receptor Splice Variants: Are they Important?

Coupar¹,

Desmond²,

Irving

2007

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“…The most recent evidence for the existence of the 5-HT 7 receptor in the rat jejunum has been obtained by the detection of mRNA transcripts encoding this receptor using a RT-PCR approach [9]. Also, we have shown that the activity profiles of antidepressants that have significant antagonist activity at guinea pig ileum 5-HT 7 receptors correlates with activity in the rat jejunum [10].…”

Section: Introductionmentioning

confidence: 79%

Influences of Gender and Region on Responses to 5-HT in the Rat Small Intestine

et al. 2004

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The aim of this study was to obtain more information regarding the ‘atypical’ 5-HT₇ receptor of the rat jejunum. 5-HT₇-induced contractions of the jejunum were elicited by 5-HT in the presence of ondansetron. Maximal responses were slightly larger in tissues from male compared to female rats of comparable age, with E_max values of 97.2 ± 3.3 and 84.25 ± 4.3% respectively compared to acetylcholine as an internal standard. However, the pEC₅₀valuesfor 5-HT were not significantly different. The mRNA expression levels of the 5-HT₇receptor were similar in whole jejunum and longitudinal muscle tissues taken from males and females. It was also shown that the maximal response of the jejunum from male rats was larger than the responses from mid intestine and ileum. However, in female tissues, the E_max of the mid intestine was significantly larger than the ileum, but not different from the jejunum. The results provide further insights into the ‘atypical’ 5-HT₇ receptor of the rat jejunum and are also useful in optimising the preparation for further studies.

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