David J. Berlove

Immunocytochemistry of a vasopressin (AVP) receptor with anti-idiotype antibody: Inhibition of staining with a peptide (PVA) encoded by an RNA that is complementary to AVP mRNA

Immunocytochemical staining of putative presynaptic (auto-) receptors associated with vasopressin (AVP) neurons by anti-idiotype antibody can be markedly reduced or abolished by preincubation of the antibody with peptide PVA. This peptide, Ser-Ser-Trp-Ala-Val-Leu-Glu-Val-Ala, represents amino acids encoded by a nucleotide sequence complementary to the mRNA code of AVP. These results suggest that PVA may have some binding characteristics similar to the AVP autoreceptor.

Co-localization of putative vasopressin receptors and vasopressinergic neurons in rat hypothalamus.

SummaryVasopressin and oxytocin are synthesized by neurons in the paraventricular and supraoptic nuclei of hypothalamus. Dense concentrations of vasopressin binding sites have also been localized in these nuclei. Using a vasopressin anti-idiotypic antiserum, a dual immunocytochemical labeling procedure has been employed to elucidate the distribution of putative vasopressin receptors in anatomical relation to vasopressin and oxytocin immunoreactive cells in rat brain. Putative vasopressin receptors are observed in relation to magnocellular neurons in hypothalamus that are vasopressin immunoreactive. They do not appear to be associated with parvocellular vasopressinergic cells or oxytocin immunoreactive neurons. The presence of these presumed autoreceptors would support evidence that vasopressin may autoregulate the activity of magnocellular vasopressinergic neurons in hypothalamus.

Staining of magnocellular neurons of the supraoptic and paraventricular nuclei with vasopressin anti-idiotype antibody: a potential method for receptor immunocytochemistry

A vasopressin anti-idiotype antibody was generated by immunization with a primary anti-vasopressin IgG. This antibody was capable of immunostaining vasopressinergic neurons in the supraoptic and paraventricular nuclei of the hypothalami of normal and Brattleboro rats. Staining was eliminated by preabsorption or coincubation of the antibody with a vasopressin binding protein prepared from rat neural membranes. The anti-idiotype also inhibited binding of [3H]vasopressin to this neural membrane protein in a dose-dependent manner. These experiments suggest that the anti-idiotype antibody recognizes a receptor associated with vasopressinergic neurons.

Immunocytochemistry of magnocellular neurons of supraoptic and paraventricular nuclei of normal and Brattleboro rats with vasopressin anti-idiotype antibody

SummaryA vasopressin anti-idiotype antibody was generated by immunization with purified IgG of a primary vasopressin antiserum. The anti-idiotype antibody immunostained neurons in the supraoptic and paraventricular nuclei of the hypothalamus of normal and Brattleboro rats. The distribution of immunostained perikarya in these hypothalamic nuclei together with the staining of fibers in median eminence and neural lobe was similar to that observed in normal rats with anti-vasopressin and suggests strongly that vasopressinergic neurons are being stained. Absorption studies with vasopressin and a vasopressin-binding receptor protein further indicate that a receptor associated with vasopressinergic neurons is recognized by the anti-idiotype antibody.

Solution-phase, parallel synthesis and pharmacological evaluation of acylguanidine derivatives as potential sodium channel blockers.

Solution-phase synthesis of various acylguanidine derivatives and the evaluation of a small library of compounds as potential sodium channel blockers are described.

Growth Factors and Brain Injury

Growth factors are generally defined as polypeptides that, at very low concentrations, act through specific receptor-mediated mechanisms to initiate and sustain complex cellular processes. These processes include cell proliferation in the case of cells capable of mitosis (such as brain glia and endothelial cells), and, in the case of post-mitotic cells such as neurons, include cell survival, outgrowth, and biochemical differentiation. An increasing number of polypeptide growth factors have been identified over the past few decades, most now grouped into several gene “superfamilies.” The identification of many of these peptides in the mammalian central nervous system (CNS) suggests that these factors play important roles in brain development, and also in the response of the mature brain to injury. Indeed, several studies have now documented increased expression of polypeptide growth factors following brain injury. Using the neurotrophin and fibroblast growth factor (FGF) superfamilies as specific examples, this review will explore two major themes: (1) that the increased “endogenous” expression of growth factors after brain injury may contribute to the cascade of cellular changes that underlie structural reorganization and functional recovery, and (2) that the “exogenous” addition of growth factors may serve to augment such recovery.

Vasopressin receptor distribution in adrenalectomized rats using vasopressin anti-idiotype

Following adrenalectomy, it has been demonstrated that parvocellular corticotropin-releasing factor-containing neurons in the paraventricular nucleus (PVN) of rat hypothalamus synthesize vasopressin. The present study examined whether putative vasopressin receptors are expressed in parallel with the appearance of vasopressin immunoreactivity in these parvocellular neurons. A vasopressin anti-idiotypic antibody which immunostains putative vasopressin receptors associated with magnocellular PVN neurons was utilized. Following adrenalectomy, antivasopressin immunostained neurons in parvocellular and magnocellular PVN, whereas the anti-idiotypic antibody immunostained magnocellular neurons only. We therefore conclude that the putative vasopressin receptor recognized by the anti-idiotype is not demonstrated in association with parvocellular vasopressin-producing neurons of the adrenalectomized rat.