Projects per year
Our research interests are the molecular genetics and functional expression of neuropeptide G protein-coupled receptors. In mammals GPCRs form the most abundant superfamily of integral membrane proteins, and it has been estimated that ~50 % of all medicinal drugs act via binding to GPCRs. We are primarily interested in the mechanisms underlying the regulation of apelin receptor (APJ) and arginine vasopressin V1b receptor gene expression and activity in the cardiovascular system, the hypothalamo-neurohypophysial system (HNS) and the hypothalamic-pituitary-adrenal (HPA) axis.
APJ and its endogenous ligand apelin are expressed in the central nervous system (CNS) and act as regulators of central and peripheral responses to multiple homeostatic perturbations including regulation of glucose homeostasis, food intake, gastric cell proliferation and angiogenesis. Many of the central effects of apelin are attributed to neuronal subpopulations of the hypothalamic paraventricular nucleus that are key structures in the regulation of endocrine and autonomic responses for the maintenance of homeostasis. We have characterised the central and peripheral distribution of APJ, where neural gene expression patterns of this receptor in the brain implicate the apelinergic system as an important regulatory axis. We have investigated the regional central activation of APJ by physiological perturbations and, using transgenic mouse models, have shown the importance of a functional APJ for maintaining water homeostasis and the HPA axis responses to stress. Studies have also revealed that APJ and apelin are present in arginine vasopressin V1b receptor-expressing cells, and that apelin’s central effects are mediated in part by regulating vasopressinergic function. We are interested in identifying APJ-dependent gene networks involved in hypothalamic plasticity and in understanding how they, and the interactions between them, are involved in controlling the body’s responses to homeostatic challenges.
In a parallel line of research we are studying the role of APJ in the central control of blood pressure and cardiovascular function in health and disease states. Apelin-APJ is extensively expressed in the central neural circuits that control blood pressure, and recent studies indicate a role for the apelin-APJ signalling pathway in basic cardiac function and during the development of hypertension. We are currently using lentiviral-driven RNA interference technology and radiotelemetry in normotensive and hypertensive rat models to determine how APJ in discrete brain regions contributes to the central control of blood pressure and to the pathogenesis of hypertension.
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- 2 Finished
11/02/16 → 29/03/19
1/02/06 → 1/02/09
Circumventricular organ apelin receptor knockdown decreases blood pressure and sympathetic drive responses in the spontaneously hypertensive ratGriffiths, P. R., Lolait, S. J., Paton, J. F. R. & O'Carroll, A-M., 4 Aug 2021, In: Frontiers in Physiology. 12, 711041.
Research output: Contribution to journal › Article (Academic Journal) › peer-reviewOpen AccessFile22 Downloads (Pure)
Kelly, E., Mathie, A., Peters, J. A., Veale, E. L., Armstrong, J. F., Faccenda, E., Harding, S. D., Pawson, A. J., Southan, C., Davies, J. A., Abbracchio, M. P., Alexander, W., Al-Hosaini, K., Bäck, M., Barnes, N. M., Bathgate, R., Beaulieu, J-M., & 135 others, 16 Sep 2021, In: British Journal of Pharmacology. 178 Suppl 1, S1, p. S27-S156 130 p.
Research output: Contribution to journal › Article (Academic Journal) › peer-reviewOpen AccessFile58 Downloads (Pure)
Increased apelin receptor gene expression in the subfornical organ of spontaneously hypertensive rats.Griffiths, P. R., Lolait, S. J., Bijabhai, A., O'Carroll-Lolait, A., Paton, J. F. R. & O'Carroll, A-M., 21 Apr 2020, In: PLoS ONE.
Research output: Contribution to journal › Article (Academic Journal) › peer-reviewOpen AccessFile6 Citations (Scopus)80 Downloads (Pure)