Relationship of Alpha-1- and Alpha-2-Adrenergic-Binding Sites to Regions of the Paraventricular Nucleus of the Hypothalamus Containing Corticotropin-Releasing Factor and Vasopressin Neurons

Abstract

To investigate catecholamine regulation of adrenocorticotropic hormone (ACTH) and vasopressin (VP) release, the relationship of alpha-adrenergic receptor-binding sites to corticotropin-releasing factor (CRF) and VP-containing cell populations within the paraventricular nucleus (PVN) of the hypothalamus was studied. Immunohistochemistry for CRF and neurophysin-vasopressin (NP-VP) was combined with receptor autoradiography. The adrenergic antagonist [³H]-prazosin was used to visualize alpha-1-binding sites and the agonist [³H]-p-aminoclonidine to visualize alphas-binding sites. To determine if changes in adrenergic binding accompanied experimentally induced increased activity of CRF-and VP-containing neurons, adrenalectomy was used as a stimulus for CRF release and dehydration as a stimulus for VP release. Quantitative assessment of autoradiograms revealed a greater density of alpha-1- and alpha-2-binding sites over the medial, parvocellular, CRF-containing region of PVN as compared to the lateral, magnocellular, NP-VP-containing region of the nucleus in all animal groups. Following 10 days of dehydration, the density of alpha-1 – and alpha-2-binding sites associated with the CRF- and NP-VP-containing regions of PVN decreased. At 14 days postadrenalectomy the density of alpha-2-binding sites associated with CRF- and NP-VP-containing regions of the nucleus decreased, but the density of alpha-1-binding sites was unchanged. Results of this study support the hypothesis that epinephrine and/or norepinephrine regulate the release of ACTH and vasopressin via alpha-1- and alpha-2-adrenergic receptors associated with CRF- and VP-containing somata within the PVN.

Removal of Adrenal Steroids from the Medium Reverses the Stimulating Effect of Catecholamines on Corticotropin Releasing Hormone Neurons in Organotypic Cultures

“…13] appears to be exerted both in vivo and in vitro through postsvnaptic alpha-1 [10,13], beta [10,21], and even alpha-2 [11,20,32] adrenergic receptors. AH of these receptor subtypes are distributed in the PVN and median eminence regions of the hypothala mus and the presence of alpha-1 and alpha-2-adrenergic receptors was clearly demonstrated on CRF-and AVPimmunopositive perikarya in the parvicellular PVN of adult rats [37], Interestingly, the density of the Cb-adrenoreceptors decreased to 45% 14 days after adrenalecto my, suggesting that the response was at least in part mediated by changes at the level of neurosecretory cells [37], Indeed, each adrenoreceptor subtype density ap pears to be differentially regulated by a variety of factors including glucocorticoid hormone level, alpha-2-subtype density being the most responsive to adrenal steroid lev els, whereas the (5-receptor number seems to be the least sensitive to these factors, and the (X|-receptor density exhibits an intermediate sensitivity [reviewed in ref. 38], Moreover, the adrenergic afferent tone may modulate adrenergic receptor density of target cells [38].…”

Presynaptic α1 Adrenergic Receptors Differentially Regulate Synaptic Glutamate and GABA Release to Hypothalamic Presympathetic Neurons

“…The PVN receives dense catecholaminergic afferents from the brainstem neurons, including the A1, A2, and A6 noradrenergic cell groups (Swanson and Sawchenko, 1983;Cunningham and Sawchenko, 1988) and C1, C2, and C3 adrenergic neurons in the rostral medulla (Cunningham et al, 1990). Receptor binding studies have shown that ␣ 1 and ␣ 2 adrenergic receptors are present in the PVN (Cummings and Seybold, 1988). Many studies have shown that ␣ 1 adrenergic receptors in the PVN play an important role in the regulation of neuroendocrine function.…”

“…Furthermore, both ␣ 1 and ␣ 2 adrenergic receptors are present in the PVN (Cummings and Seybold, 1988). Microinjection of norepinephrine into the PVN raises the blood pressure in rats, and this effect is because of, in part, the release of arginine vasopressin (Harland et al, 1989).…”

The Role of Alpha-2-Adrenoceptors in the Control of ACTH Secretion; Interaction with the Opioid System

“…In the central nervous system, alpha-2-adrenoceptors are found in the regions that contain the cell bodies of the adrener gic and noradrenergic neurones, and in the areas to which these neurones project, including the hypothalamic paraventricular nucleus [30. 44], Alpha-2-receptor binding sites are found in the regions of the paraventricular nucleus that are immunoreactive to CRF-41 and vasopressin neurophysin [14], These recep tors are located both presynaptically (on the noradrenergic neurone) and postsynaptically (on the target neurone) [45], In both cases, activation of these receptors inhibits the firing of the neurone [11, 26]. When the neurones are firing, activation of presynaptic alpha-2-adrenoceptors is believed to act as a nega tive feedback mechanism, whereby noradrenaline limits its own release [ 1 ].…”