Mechanisms associated with secretory and contractile responses in tissues and cells of the body in health and disease

Abstract

Volume 1 (A/B) of the thesis investigated the innervation pattern, the cellular mechanism(s) of stimulus-secretion coupling (SCC), the effects of age and the in eraction between calcium and magnesium signalling in secretory cells taken from the thyroid gland, the parotid land, the ancreas, the stomach and the lacrimal gland. 1n addition, the study investigated the roles of anti-ulcer and anti-secretory drugs in the stomach and calpains in relation to vision. The study was designed to understand diseased states ( eg diabetes mellitus, pancreatitis, gastric ulcers, cataractogenisis and the dry eye syndrome) compared to healthy conditions. The results have demonstrated that, in addition to parasympathetic nerves, the pancreas, parotid and the lacrimal glands are innervated with adrenergic and non-cholinergic, non-adrenergic (peptidergic) nerves. Stimulation of these intrinsic secretomotor nerves can result in the secretion of proteins and enzymes from the pancreas, the parotid and lacrimal glands. Exogenous application of either acetylcholine (ACh), noradrenaline (NA), or a number of neuropeptides (vasoactive intestinal peptide (VIP), substance P, neuropeptide Y (NPY) and several others), can elicit protein and enzyme secretion. Apart from nervous control, exocrine pancreatic secretion is regulated by both endocrine and paracrine hormones. Cholecystokinin-octapeptide (CCK), secretin and histamine can stimulate protein and enzyme secretion from the pancreas. In addition to innervation pattern, this study also investigated the cellular mechanisms of stimulus-secretion coupling. The results have shown that there are four functionally distinct intracellular signalling pathways via which secretagogues (neurotransmitters, hormones and drugs) can elicit their responses in secretory epithelial cells. These include the utilization of such second messengers as calcium (Ca2+), adenosine 3, 5 cyclic monophosphate ( cyclic AMP), protein kinase C (PKC) and tyrosine kinase (TK . A combination of these intracellular messengers can either potentiate or attenuate on