Jaya Haldar

Oxytocin and Vasopressin are Present in Human and Rat Pancreas

Immunoreactive oxytocin and vasopressin were found in human and rat pancreatic extracts. The pancreatic oxytocin and vasopressin eluted on Sephadex G-75 gel filtration chromatography and on reverse phase high pressure liquid chromatography in the same positions as their respective reference preparations. The immunoreactive oxytocin was biologically active in the rat milk ejection assay. The presence of oxytocin and vasopressin in human and rat pancreatic extracts suggests the possibility of local synthesis of both hormones. The neurohypophysial hormones are known to be endocrine mediators of insulin and glucagon release. The finding of oxytocin and vasopressin in the pancreas raises the possibility, although yet unproven, of local synthesis and perhaps a paracrine function for the neurohypophysial peptides upon pancreatic hormone release or for a local function upon the liver.

Vasopressin Concentrations in Hypophysial Portal Plasma: Insignificant Reduction following Removal of the Posterior Pituitary Gland

This study was designed to determine the relative contribution of vasopressin-secreting nerve terminals in the median eminence compared to those in posterior pituitary to the high concentrations of the hormone in hypophysial portal blood. Vasopressin was measured by radioimmunoassay in plasma obtained by microcannulation of individual long portal veins of 8 intact male Long-Evans rats (2.0 +/- 0.44 ng/ml SEM), and in 8 in which the posterior pituitary was removed just prior to collection (1.5 +/- 0.3 ng/ml SEM). Since there was no significant difference /p = 0.23, NS) in the concentration of vasopressin in portal plasma after removal of the posterior pituitary gland, these results suggest that the direct vasopressin pathway to the median eminence is the major source of vasopressin in portal blood of the rat.

Elimination of vasopressin analgesia following lesions placed in the rat hypothalamic paraventricular nucleus

Pain thresholds are increased following central administration of arginine vasopressin (AVP), an effect which appears not to be mediated through opioid analgesic processes. In addition to magnocellular projections to the posterior lobe of the pituitary gland and parvocellular projections to the zona externa of the median eminence, the paraventricular nucleus (PVN) of the hypothalamus contains VP parvocellular neurons which also project to extrahypothalamic structures involved in pain inhibition. The present study examined whether AVP analgesia as measured by the tail-flick test was altered in animals with lesions placed in the PVN at either 7 or 35 days after surgery. VP levels in the pons-medulla and the lumbo-sacral spinal cord were measured by radioimmunoassay, as well as VP-like immunoreactivity in the PVN and spinal cord with immunocytochemistry. Lesions placed in the PVN eliminated AVP analgesia on the tail-flick test at both 7 and 35 days after surgery, and decreased radioimmunoassayable VP by 59% in the lumbo-sacral spinal cord and 36% in the pons-medulla. The extent of the lesions ranged from complete destruction of the PVN to partial sparing of ventro-medial PVN cells with VP-like immunoreactivity. These data indicate that the PVN is a critical structure for the integrity of AVP analgesia.

Immobilization stress affects oxytocin and vasopressin levels in hypothalamic and extrahypothalamic sites.

Oxytocin (OT) and vasopressin (VP) have been localized in various sites within the central nervous system outside the classic hypothalamo-neurohypophyseal axis. This study investigated the effect of immobilization stress on the levels of OT and VP in the hypothalamus, pons-medulla, and the cervical, thoracic, and lumbosacral segments of the spinal cord. Male Long Evans rats were immobilized for 1 min and sacrificed by guillotine. The tissues were dissected out and homogenized in 0.1 N HCl. The hormone content was determined by radioimmunoassay (RIA) in Sep-pak extracted samples. The data show a decrease in OT content of 33.6% (P less than 0.02) and 42.4% (P less than 0.01) in the hypothalamus and pons-medulla, respectively. In the spinal cord, however, OT levels were increased by 39.1% (not significant), 51.1% (P less than 0.05), and 87.6% (P less than 0.001) in the cervical, thoracic, and lumbosacral segments respectively. The VP content of the hypothalamus and pons-medulla did not change. However, in the spinal cord, the VP content was also increased by 101.4% (P less than 0.01) and by 143.7% (P less than 0.01) in the cervical and lumbosacral segments. The levels of VP in the thoracic segment did not change. The data demonstrate that stress can alter hypothalamic and extra-hypothalamic levels of OT as well as spinal cord levels of VP. The exact physiological effects of these changes, particularly within the spinal cord, remain to be elucidated.

Extrahypothalamic neurohypophysical peptides in the rat central nervous system

Abstract Vasopressin (VP) and oxytocin (OT) have been identified in a number of extrahypothalamic areas, both by immunohistochemistry and by radioimmunoassay. Because of the incomplete nature of the data available, we have conducted a survey of the VP and OT concentrations in the rat central nervous system. VP and OT were readily detectable in all areas studied. With the exception of the amygdala, OT concentrations were generally 2–4 times those of VP. The physiological function of neurohypophysial hormones in these extrahypothalamic areas is essentially unknown.

Isotonic and hypertonic saline act as stressful stimuli for oxytocinergic system of the pituitary, hypothalamus and spinal cord.

We have recently demonstrated that immobilization stress leads to an increase in the spinal cord oxytocin content in the rat. The current experiments were undertaken to determine if other stressors have similar effect on the spinal cord oxytocin levels. Male Long Evans rats were injected either with isotonic or hypertonic saline and sacrificed either 15 minutes or 3 hours after saline injection. Oxytocin content of the neurohypophysis, hypothalamus and spinal cord were determined by specific radioimmunoassay in Sep-pak extracted samples. The results demonstrate that both isotonic and hypertonic saline act as stressful stimuli and reduce oxytocin content of the pituitary and hypothalamus when the rats were sacrificed within 15 minute following the injection. Spinal cord oxytocin content was also affected by isotonic and hypertonic saline administration; oxytocin content decreased if rats were sacrificed after a short period (15 min) and increased if rats were sacrificed after a long period (3 hours). These results, together with those reported earlier, support the hypothesis that stressors, in general, affect the spinal cord oxytocin content.

Opioid modulation of oxytocin release from spinal cord synaptosomes

Regulation of oxytocin release from spinal cord synaptosomes was investigated using in vitro preparations. Experiments were designed to determine whether opioid peptides regulate oxytocin release from spinal cord synaptosomes, as they do from synaptosomes derived from neurohypophysis. Oxytocin release was evoked by the addition of 56 mM KCl in synaptosomes prepared from thoracic and lumbosacral parts of the spinal cord. Addition of 5 microM naloxone, 1 min prior to the addition of the stimulus, caused a significant (p < 0.025) increase of oxytocin release. Prior addition of 5 microM dynorphin, demonstrated a significant (p < 0.01) decrease whereas addition of 5 microM [D-Ala2,N-Me-Phe4,Gly-ol]-enkephalin showed no effect on KCl-induced OT release. The results suggest that spinal cord OT release is under inhibitory control of opioid peptides and the opioids act via the kappa opioid receptor.

Hypothalamic oxytocin: a cerebrovascular modulator in man?

Immunocytochemical studies in normal rats show an association between oxytocin (OT) neurons and cerebral blood vessels. This is supported by the finding of neurophysin (NP) immunoreactivity in blood vessels and piaarachnoid tissue of rats with hereditary vasopressin (VP) and VP-NP deficiency. OT and OT-NP fibers were visualized in pia-arachnoid and blood vessels at the base of the brain and, to a lesser extent, over the dorsal surface. OT constricts human basilar artery with a threshold response in the 10 10 M range, and an ED50 of 4.8 × 10 9 M. These observations suggest that extrahypothalamic projections of OT neurons may modulate cerebrovascular function.

Effects of Cysteamine on Blood Pressure: Possible Mediation through Vasopressin Release

Abstract Cysteamine (β-mercaptoethylamine, CSH) has been reported to have various effects on the neuroendocrine system. Reports indicate CSH decreases pituitary oxytocin (OT) without affecting pituitary vasopressin (VP). However, preliminary studies from our laboratory strongly indicate that CSH has an effect on VP release. Experiments were conducted with dibenzyline-treated, urethane-anesthetized, male Sprague-Dawley (SD) rats. Rats were injected with 4 mU of standard VP and 4 mg/100 g of CSH. Administration of VP resulted in an increase in mean arterial pressure (MAP) of 23.5 ± 3.2 mm Hg. Administration of CSH resulted in a consistent. immediate decrease in MAP of 13.0 ± 2.0 mm Hg prior to an increase of 21.0 ± 2.6 mm Hg. The effects due to VP and CSH were strikingly different; the CSH-induced MAP rise took longer to peak and to return to baseline. Both the VP- and CSH-induced MAP rise were markedly inhibited by a prior administration of a specific VP antagonist d(CH2)5[Tyr(Me)]AVP. In addition, the typical increase in MAP observed in SD rats following CSH administration was substantially reduced when the same dose was administered in homozygous diabetes insipidus (HODI) rats. The data presented here strongly suggest that CSH-induced MAP elevation is due to the release of VP from the pituitary gland.

The release of oxytocin from spinal cord synaptosomes by high KCL depolarizing stimulus: A calcium dependent process☆

Oxytocin (OT) release from synaptosomes isolated from the thoracic (T) and lumbosacral (LS) regions of the spinal cord was evoked by 56 mM potassium chloride (KCl). The release mechanism was shown to be a calcium dependent process. The ability of high KCl to evoke OT release from isolated nerve terminals in a calcium dependent manner provides additional support for the role of OT as a neurotransmitter in the spinal cord.