The role of the muscarinic system in regulating estradiol secretion varies during the estrous cycle: the hemiovariectomized rat model

There is evidence that one gonad has functional predominance. The present study analyzed the acute effects of unilateral ovariectomy (ULO) and blocking the cholinergic system, by injecting atropine sulfate (ATR), on estradiol (E(2)) serum concentrations during the estrous cycle. The results indicate that ULO effects on E(2 )concentrations are asymmetric, vary during the estrous cycle, and partially depend on the cholinergic innervation. Perforation of the left peritoneum resulted in lower E(2 )serum concentrations in the three stages of the estrous cycle. At proestrus, unilateral or bilateral perforation of the peritoneum resulted in lower E(2 )serum concentrations. ULO of the right ovary (left ovary in situ) resulted in significantly higher E(2 )concentrations than animals with ULO of the left ovary (right ovary in situ). ATR treatment to ULO rats on D1 resulted in a significant drop of E(2 )serum concentrations. ULO rats treated with ATR on D2 or P, resulted in an asymmetrical E(2) secretion response; when the right ovary remained in situ an increase in E(2) was observed, and a decrease when the left ovary remained in situ. The results obtained in the present study suggest that each ovary's ability to compensate the secretion of E(2 )from the missing ovary is different and varies during the estrous cycle. The results also suggest that the cholinergic system participates in regulating ovarian E(2 )secretion. Such participation varies according to the ovary remaining in situ and the stage of the estrous cycle of the animal. The results agree with previously stated hypothesis of a neural pathway arising from the peritoneum that participates in regulating E(2 )secretion, and also supports the idea of cross-talk between the ovaries, via a neural communication, that modulates E(2 )secretion

Autoradiographic localization of [3H]muscimol binding sites in rat stomach: evidence for mucosal GABAA receptors.

The distribution in the rat stomach of specific [3H]muscimol binding sites, which show characteristics of GABAA receptors, was examined by light microscopic autoradiography. Silver grains representing specific binding were present both in the antrum and body, with highest densities in the muscle layers. A small fraction of the binding was confined to gland cells of the mucosa in the gastric body, rather than in the antrum. The label was not specifically concentrated at the myenteric ganglia. These findings, along with earlier data, suggests that the local GABA content may regulate not only the contractility, but also the secretory functions of the stomach via gastric GABAA receptors

Autoradiographic localization of the GABAA receptor agonist [3H]-muscimol within rat kidney

By the use of combined radioreceptor binding and autoradiographic techniques, the pharmacological characteristics of (3H)-muscimol binding and the localization of the label were studied. (3H)-Muscimol was bound by sections of rat kidney in a manner consistent with the existence of specific gamma-aminobutyric acid 'A' (GABAA) receptors with KD and Bmax values of 23.7 nmol/l and 1.15 pmol/mg tissue, respectively. (3H)-Muscimol was bound by convoluted tubules of the renal cortex and by the collecting tubules. Our findings demonstrating the existence of recognition sites for the GABAA receptor agonist muscimol in the kidney suggest that GABA has a role in renal function

Autoradiographic localization of the GABAA receptor agonist [3H]-muscimol within rat kidney

By the use of combined radioreceptor binding and autoradiographic techniques, the pharmacological characteristics of (3H)-muscimol binding and the localization of the label were studied. (3H)-Muscimol was bound by sections of rat kidney in a manner consistent with the existence of specific gamma-aminobutyric acid 'A' (GABAA) receptors with KD and Bmax values of 23.7 nmol/l and 1.15 pmol/mg tissue, respectively. (3H)-Muscimol was bound by convoluted tubules of the renal cortex and by the collecting tubules. Our findings demonstrating the existence of recognition sites for the GABAA receptor agonist muscimol in the kidney suggest that GABA has a role in renal function

Binding of antibodies in sera from Type 1 (insulin-dependent) diabetic patients to glutamate decarboxylase from rat tissues. Evidence for antigenic and non-antigenic forms of the enzyme

An islet protein of Mr 64000, identified as the γ-amino butyric acid (GABA)-synthesizing enzyme, glutamate decarboxylase, is a major target for antibodies in Type 1 (insulin-dependent) diabetes mellitus. This enzyme is also expressed in brain and in some other tissues and may exist in multiple forms. The aim of this study was to determine the ability of antibodies from diabetic patients to recognize glutamate decarboxylase from rat islets, brain and other normal rat tissues. Glutamate decarboxylase was detected at high activity levels in brain and at lower levels in islets, kidney, liver, pituitary gland, thyroid gland, adrenal gland, testis and ovary. The ability of antibodies in sera of diabetic patients to immunoprecipitate enzyme activity from detergent extracts of tissues was determined. Antibodies in sera from diabetic patients were found to bind the enzyme from islet and brain extracts, but bound less than 20% of the activity from other tissues. The ability of antibodies to immunoprecipitate the brain enzyme was significantly correlated with the presence of antibodies to the islet 64 kilodalton antigen. These studies show that the glutamate decarboxylase activity expressed in brain shares antigenic determinants with the islet 64 kilodalton antigen. Isoforms of the enzyme expressed in other nonneuronal tissues may be antigenically distinct and may lack determinants recognized by diabetes-associated antibodies

Localization of GAD-like immunoreactivity in the pancreas and stomach of the rat and mouse

The aim of this study was to localize cells immunoreactive for glutamate decarboxylase (GAD), the enzyme of GABA synthesis, in pyloric and oxyntic regions of the rat stomach as well as in the rat and mouse pancreas. GAD immunocytochemistry was carried out on polyethylene glycol or cryostat sections of alkaline paraformaldehyde fixed tissue, with simultaneous immunolabelling of various gastro-pancreatic hormones for topographical comparison. In the rat stomach, nerve fibers displaying intense GAD-like immunoreactivity were seen in the myenteric plexus, the circular muscular layer, the submucosa and the lamina propria of the mucosa. But, they were absent from the submucous plexus. Colchicine treatment of the rats allowed to detect some labelled perikarya in the myenteric plexus suggesting that the GABAergic innervation is at least partly intrinsic to the stomach. In the oxyntic and pyloric mucosa, endocrine cells appeared immunostained for GAD. However, the nature of their hormones remained unknown since double immunodetections revealed that they were immunoreactive neither for gastrin nor for somatostatin. In the rat and mouse pancreas, GAD-like immunoreactivity was found in islet cells which corresponded only to insulin-secreting cells. Somatostatin-, glucagon- and pancreatic polypeptide-immunopositive cells were devoid of GAD immunolabelling. No GAD-like immunoreactivity was detected in the exocrine tissue and innervation. These results strenghten the hypothesis that GABA is not only a neurotransmitter in the stomach but that it could also be an endocrine or paracrine factor in the stomach and pancreas

Immunocytochemical and autoradiographic studies of the endocrine cells interacting with GABA in the rat stomach

There are now increasing evidences suggesting that GABA is able of direct interaction with certain endocrine cells. In the present study, highly specific anti-GABA-glutaraldehyde antibodies and 3H-GABA uptake were used at the light and electron microscope levels to investigate the occurrence of cells containing endogenous GABA or taking up exogenous GABA in the mucosal antrum and corpus of the rat stomach. Only certain endocrine cell types of both regions were immunostained or grain-labelled. However, the morphology of their secretory granules did not allow to identify the nature of their hormone with certainty but suggested that somatostatin-like cells could interact with GABA. The combination of gastrin and somatostatin immunodetection with 3H-GABA uptake autoradiography at the light microscope level, revealed that a subpopulation of somatostatin-like cells and other still unidentified endocrine cells are able to take up GABA, while the gastrin-like cells are not. These results reinforce the hypothesis that certain endocrine cell types of the diffuse endocrine system of the digestive tract are able to directly interact with GABA