Catecholamine secretion regulation

Pituitary Adenylyl Cyclase-activating Polypeptide (PACAP) is a 38-amino acid peptide (PACAP-38), which is widely expressed in the central nervous system. PACAP is most abundant in the hypothalamus. It is also found in the gastrointestinal tract, the adrenal gland and in testis. Its central nervous system functions are ill-defined. In the periphery, PACAP has been shown to stimulate catecholamine secretion from the adrenal medulla and to regulate secretion from the pancreas. Three G-protein coupled receptors have been shown to respond to PACAP, PAQ (PACAP type I) specifically binds PACAP, VPACi and VPAC2 also bind vasoactive intestinal peptide (VDP). Activation of PACAP receptors results in a Gs-mediated activation of adenylyl cyclase. 

Matsuzawa, A., Makoto, M., Atsumi, G. et al. Release of secretory phosphohpase A2 from rat neuronal cells and its possible function in the regulation of catecholamine secretion. Biochem. J. 318,701-709,1996. 

The catecholamines epinephrine and norepinephrine (adrenaline and noradrenaline) originate in the inner medullar region of the adrenal glands. Stimulation of the adrenal by the sympathetic nervous system leads to secretion of catecholamines into the bloodstream. In addition, adipose tissue is itself directly innervated by the sympathetic nervous system. Various types of metabolic stress trigger the sympathetic nervous system to release its neurotransmitter, norepinephrine, directly into adipose where its effects on the adipocyte are mediated by specific plasma membrane adrenoreceptors. Rapid reflex responses are primarily stimulated by the sympathetic nervous system, whereas more long-term (i.e., on the scale of hours, days, and weeks) and/or basal effects are subject to regulation by catecholamine secretion. 

The functional importance of this pathway in regulating adrenal cortical and medullary functions is not clear. Cyclic GMP has been implicated in both steroidogenesis (Sharma etal. 1974, 1976, Per-CHELLET et al. 1978, Perchellet and Sharma 1979) and catecholamine secretion (Derome et al. 1981, Dohi et al. 1983, O Sullivan and Burgoyne 1990). 

The adrenal gland is located on the upper segment of the kidney (Fig. 42-1). It consists of an outer cortex and an inner medulla. The adrenal medulla secretes the catecholamines epinephrine (also called adrenaline) and norepineprhine (also called noradrenaline), which are involved in regulation of the sympathetic nervous system. The adrenal cortex consists of three histologically distinct zones zona glomerulosa, zona fasciculata, and an innermost layer called the zona reticularis. Each zone is responsible for production of different hormones (Fig. 42-2). 

Effect on endocrine function Catecholamines are important endogenous regulators of hormone secretion from a number of glands. Insulin secretion is stimulated by beta receptors and inhibited by a2-receptors. Similarly, renin secretion is stimulated by Pj and inhibited by receptors indeed, beta-receptor antagonists may lower plasma renin at least part by this mechanism. 

However, receptor autoradiography and in vitro studies have suggested that H3 receptors are located on other aminergic neurons in the brain. Since amines such as serotonin and catecholamines are involved in the regulation of pituitary hormone secretion, it is obvious that an action of the H3 receptor compounds may be exerted via these H3 heteroreceptors. Only few studies have evaluated this heteroreceptor action. It has been excluded that the effect of the H3 receptor agonists is due to an effect on H3 receptors located on serotonergic neurons, while an effect on catecholaminergic neurons has yet not been excluded. 

Andersson K, Eneroth P (1987) Thyroidectomy and central catecholamine neurons of the male rat. Evidence for the existence of an inhibitory dopaminergic mechanism in the external layer of the median eminence and for a facilitatory noradrenergic mechanism in the paraventricular hypothalamic nucleus regulating TSH secretion. 

Barraclough CA, Wise PM (1982) The role of catecholamines in the regulation of pituitary luteinizing hormone and follicle-stimulating hormone secretion. Endocrine Rev 5 91-119. 

Although often considered a part of the sympathetic nervous system, the adrenal meduUa produces and secretes a different catecholamine, epinephrine, with different functions from the norepinephrme secreted by sympathetic nerves, The adrenal medulla and sympathetic nerves are also regulated separately, often in divergent directions in response to different forms of stress. 

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