Research Interests

• autonomic neuroeffector mechanisms and receptor pharmacology, particularly of adrenoceptors. 
• generic mechanisms underlying how autonomic neurotransmitters and their receptors work to control several major body systems, via the autonomic nervous system: cardiovascular, urogenital and respiratory systems. 
• how malfunction of these mechanisms contributes to diseases and the ageing process and how drugs can reverse this. 

British Journal of Pharmacology. The front cover illustrations is used for each issue (12) throughout the year. The volumes below are for 2004 (left), 2005 (middle) and 2007 (right). 2004 shows alpha1-adrenoceptor distribution in liver cells. 2005 shows alpha1-adrenoceptors in two smooth muscle cells isolated from a human skeletal artery. 2007 shows alpha1-adrenoceptors and agiotensinII receptors on the endothelial cells of a mouse aorta.

Our group have become specialists in using 3D imaging for studying blood vessel structure and function.

**Recent Publications**

Morton, JS, Jackson VM, Daly CJ & McGrath JC (2007). Endothelium dependent relaxation in rabbit genital resistance arteries is predominantly mediated by endothelial-derived hyperpolarizing factor in females and nitric oxide in males. J Urol. 2007 Feb;177(2):786-91.

Nasuti C, Cantalamessa F, Daly CJ & McGrath JC (2007). Alterations in rabbit aorta induced by types I and II Pryrethroids. Exp. Toxicol & Pharmacol. 23:250-253.

Morton, J.S.; Daly, C.J.; McGrath, J.C.; Jackson, V.M. (2005). Development of an in vitro method to study vaginal arteries using myography. Br J Pharmacol. 2007 Jan;150(1):112-20.

Papay R, Gaivin R, Jha A, McCune DF, McGrath JC, Rodrigo MC, Simpson PC, Doze VA, Perez DM. Localization of the mouse alpha1A-adrenergic receptor (AR) in the brain: alpha1AAR is expressed in neurons, GABAergic interneurons, and NG2 oligodendrocyte progenitors. J Comp Neurol. 2006 Jul 10;497(2):209-22.

Jamila Ibrahim, Ann McGee, Delyth Graham, John C. McGrath, and Anna F. Dominiczak. Sex-specific differences in cerebral arterial myogenic tone in hypertensive and normotensive rats. Am J Physiol Heart Circ Physiol. 2006 Mar;290(3):H1081-9

Ana M. Briones, Craig J. Daly, Francesc Jimenez-Altayo, Sonia Martinez-Revelles, Jose M. Gonzalez, John C. McGrath & Elisabet Vila (2005) Direct demonstration of b1- and evidence against b2- and b3-adrenoceptors, in smooth muscle cells of rat small mesenteric arteries Br J Pharmacol 146:679–691

Deighan C, Methven L, Naghadeh MN, Wokoma A, Macmillan J, Daly CJ, Tanoue A, Tsujimoto G and McGrath JC (2005) Insights into the functional roles of alpha1-adrenoceptor subtypes in mouse carotid arteries using knockout mice. Br J Pharmacol - 144, 558-565

Miquel, MR., Ali, Z., Segura V., D'Ocon, MP McGrath, JC & Daly, CJ. (2005). 3D image analysis of fluorescent drug binding. Molecular Imaging. Vol 4 No. 1; 1-13.

McGrath JC & Daly CJ. The use of fluorescent ligands and proteins to visualise adrenergic receptors (2005) In: The Adrenergic Receptors in the 21st Century: The Receptor Series. Volume Editor: Dianne M. Perez: Series Editor: Kim Neve. Humana Press, Inc., Part 3; Chapter 6, pages 151-172

John Daniel Pediani, Janet Fraser Colston, Darren Caldwell, Graeme Milligan, Craig James Daly, and John Christie McGrath (2005) beta-arrestin Dependent Spontaneous alpha1a-Adrenoceptor Endocytosis causes Intracellular Transportation of alpha-blockers via Recycling Compartments. Molecular Pharmacology. 67; 992-1004.

Hamid S.A., Howe D., Campbell S., & Daly CJ. (2005) Visualisation of morphological changes in living intact human microvessels using confocal microscopy. Microvascular Research. Volume 69, Issue 3, May 2005, Pages 173-177

Daly CJ & McGrath JC (2005) The role of the alpha1B-adrenergic receptor in vascular structure and function. Hypertension. In Press.

Shafaroudi MM, McBride M, Deighan C, Wokoma A, Macmillan J, Daly CJ & McGrath JC (2005) Two knockout mouse models demonstrate that aortic vasodilatation is mediated via a2A-adrenoceptors located on the endothelium. J. Pharmacol Ther; 314; 804-810.

McGrath JC, Deighan C, Briones AM, Arribas SM, Vila E & Daly CJ. (2005) New aspects of vascular remodelling: the involvement of all vascular cell types. Experimental Physiology, 90.4: 469-475

Gonzalez JM et al., (2005) Influence of elastin on rat small artery properties. Experimental Physiology, 90.4; 463-468

Zacharia, J., Hillier, C., Tanoue, A., Tsujimoto, G., Daly C.J., McGrath, J.C. & MacDonald, A. Evidence from knockout mice for involvement of a1D-adrenoceptors in contraction of femoral resistance arteries. (2005). Br. J Pharmacol. British Journal of Pharmacology 146, 7; 942-951

About our Research

The Work of The Lab. The core interests of the APU group are autonomic neuroeffector mechanisms and receptor pharmacology, particularly of adrenoceptors. This is focussed mainly on how these work to control the cardiovascular system and how they malfunction in cardiovascular disease particularly hypertension, heart failure and stroke. The group has a growing and rekindled interest in human prostate and vas deferens respectively. 

The lab's approach lies in the combination of classical functional pharmacological methods with visualisation of the structure of small multicellular tissues and the location of receptors, using advanced microscopic and image analysis methods. We work up techniques on cultured cells, particularly those transfected with well-defined recombinant receptors, in order to validate new methods for application to tissues, particularly human tissue. We have developed methods using fluorescent ligands to localise adrenoceptors in individual cells and in blood vessels. This has allowed quantification of drug-receptor interactions at the subcellular level and has uncovered functional binding of intracellular receptors providing an important new concept for drug targetting (420, 423). 

This fundamental work is applied to understanding how disease can alter these processes directly or indirectly to cause functional and chronic structural changes to autonomic nerves, smooth muscle and other cells that interact with them. 

This knowledge is then applied to understanding whether these changes can be prevented or reversed by drug treatment. Since fundamental mechanisms are imprecisely understood, drugs are often used as a tool in eliciting fundamental mechanisms. This symbiotic relationship in using drugs to understand fundamental mechanisms and vice versa is central to our work. In the last five years we have also used genetics in an analogous way to manipulate receptors and related mechanisms (e.g. 440). 

[References available from the APU publications list]