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W K Samson

Publications and source records attributed to W K Samson.

At least 37 records · Page 2Linked to original sources
PubMed1998

Central mechanisms for the hypertensive effects of preproadrenomedullin-derived peptides in conscious rats.

Peptides derived from postranslational processing of preproadrenomedullin exert potent hypotensive effects in the periphery. One of those peptides, adrenomedullin (AM) also has been demonstrated to act centrally in conscious rats to inhibit water drinking and salt appetite and, in anesthetized rats, surprisingly to increase blood pressure. We examined the effects of AM and the other postranslational product, proadrenomedullin NH2-terminal 20 peptide (PAMP), on blood pressure in conscious rats. Both AM and PAMP elicited dose-related increases in mean arterial pressure after cerebroventricular administration. The hypertensive effects of both AM and PAMP and of ANG II were blocked by peripheral administration of phentolamine, indicating actions of the peptides in brain to stimulate sympathetic nervous system function. Blockade of central ANG II receptors with saralasin prevented the hypertensive effects of both ANG II and PAMP, suggesting recruitment of endogenous angiotensinergic systems by central PAMP. The structural homolog of AM, calcitonin gene-related peptide (CGRP), at similar doses did nto significantly affect blood pressure. Furthermore, the hypertensive effects of ANG II, AM, and PAMP were not abrogated by prior administration of the CGRP antagonist. We hypothesize that AM and PAMP exert cardioprotective effects in brain, which may counterbalance the volume-unloading actions of the peptides in the periphery.

Adrenomedullin↗
PubMed1998

Proadrenomedullin N-terminal 20 peptide inhibits adrenocorticotropin secretion from cultured pituitary cells, possibly via activation of a potassium channel.

Preproadrenomedullin is processed into at least two biologically active peptides, adrenomedullin (AM) and proadrenomedullin N-terminal 20 peptide (PAMP). Both peptides are hypotensive; however, they exert this action via differing mechanisms. In pituitary cells in culture, both basal and releasing factor-stimulated adrenocorticotropin (ACTH) secretion is inhibited by AM. Here we report that basal, but not stimulated, ACTH secretion from cultured rat pituitary cells is also inhibited by PAMP. The effect is dose-related, occurs in a physiologically relevant dose range that is similar to that of AM, and is blocked by the potassium channel blocker, glybenclamide. The failure of glybenclamide to inhibit AM's effects on ACTH secretion indicates that in pituitary, as in other tissues, these two products of the same prohormone can exert similar biologic activity, although via differing mechanisms.

Adenosine Triphosphate↗
PubMed1998

Gender-biased activity of the novel prolactin releasing peptides: comparison with thyrotropin releasing hormone reveals only pharmacologic effects.

The prolactin- (PRL) releasing activities of the newly described PRL-releasing peptides (PrRPs) were compared to that of thyrotropin-releasing hormone (TRH) in dispersed, rat anterior pituitary cell cultures. A dose-related stimulation of PRL release by TRH was observed in cells harvested from both intact male and random cycle female pituitary donors. The minimum effective dose of TRH ranged from 1 to 10 nM. Neither PrRP-20 nor PrRP-31 significantly altered PRL secretion in cells from male donors even at doses as high as 1 microM. In cells harvested from females, only the highest doses of PrRP-20 and PrRP-31 tested (0.1 and 1.0 microM) significantly stimulated PRL secretion. The PRL-releasing action of TRH was observed already at 15 min of incubation, whereas those of PrRP-20 and PrRP-31 appeared only after 1 and 2 h of incubation, and the magnitude of PRL release in the presence of 1 microM PrRPs was significantly less than that of a similar dose of TRH. These data do not suggest a physiologically relevant role for the PrRPs in the neuroendocrine regulation of PRL secretion in intact male and nonlactating, random-cycle female rats.

Animals↗
PubMed1997

Adrenomedullin inhibits salt appetite.

Adrenomedullin (AM) exerts profound natriuretic and vasodilatory effects in conscious animals. This newly discovered hormone also acts in the central nervous system to inhibit water drinking and in the pituitary gland to reduce basal and stimulated ACTH release. We investigated whether the natriuretic action of AM in kidney was matched by a central nervous system action to decrease salt intake. Isotonic hypovolemia induced in male rats by pretreatment with polyethylene glycol potently stimulates both water and salt water (0.3 mol/liter NaCl) drinking. Saline drinking was significantly inhibited when AM was administered into the lateral cerebroventricle before the drinking interval. The effect was dose related (dose range, 44-88 pmol), long lasting (> 5 h), and reversible (resolved at 24 h). When hypovolemic rats were administered antiserum to AM (intracerebroventricular administration) before the drinking interval, a significant 2-fold augmentation of saline drinking was observed. These data suggest that in addition to peripheral actions on cardiovascular and renal function and pituitary actions to inhibit ACTH release, AM may act within the central nervous system to determine fluid and electrolyte balance and, ultimately, blood pressure.

Adrenomedullin↗
PubMed1996

A 35 amino acid fragment of leptin inhibits feeding in the rat.

Peptide fragments of the larger 167 amino acid obesity gene related peptide (OBGRP), leptin, were tested for their ability to inhibit feeding in the rat. The C-terminal fragment, OBGRP 116-167 exerted only minimal inhibition of feeding when administered into the lateral cerebroventricle. No alteration in feeding was observed following administration of OBGRP 57-92. We hypothesized that the satiety effects of leptin reside in the N-terminal region of the peptide sequence. Significant, dose-related, and reversible inhibition of food intake was observed following central administration of the 35 amino acid fragment OBGRP 22-56. These results suggest that a small, readily synthesized fragment of the 167 amino acid peptide leptin may exert physiologically relevant satiety effects in brain revealing an endocrine feedback mechanism by which the adipocyte may modulate hypothalamic function.

Amino Acid Sequence↗
PubMed1996

Calcitonin is a physiological inhibitor of prolactin secretion in ovariectomized female rats.

Calcitonin (CT) inhibits secretion of PRL when administered intravenously in rats and humans. It also inhibits PRL release from cultured rat anterior pituitary (AP) cells. Recent evidence suggests that CT-like immunoreactive peptide is synthesized and released from the AP gland. However, its physiological role in the regulation of PRL secretion has not been understood. Present studies tested the role of endogenous pituitary CT (pit-CT) in the regulation of PRL secretion in vivo by passive immunization. In the first group of experiments, ovariectomized (ovx) adult female rats were administered either preimmune or anti-salmon CT (sCT) serum, and their serum PRL levels were analyzed at various time points up to 3 h. A second group of experiments examined the effects of anti-sCT serum and dopamine on PRL release from cultured rate AP cells. In the next group of experiments, the regional distribution of pit-CT secretion was examined in different sections of the AP gland. In the last set, CT-like activity of AP extract was tested in neonatal rat kidney cells, which respond to CT with an increase in cAMP accumulation. These experiments also tested whether anti-sCT serum reduces AP extract-induced increase in cAMP accumulation. The results suggest that anti-sCT serum dramatically increased serum PRL levels (by 5-fold) of ovx rats within 30 min of administration. The serum PRL levels declined gradually after the peak. However, a significant increase in serum PRL levels was maintained by the anti-sCT serum for the duration of the experiment. The anti-serum also induced a significant increase in PRL release from cultured AP cells when added to the presence or absence of dopamine. The distribution profile of pit-CT within the AP gland suggests that the release of pit-CT immunoreactivity was significantly greater in the inner sections, and anti-sCT serum also caused greater increase in PRL release in these sections. Finally, AP extract and sCT stimulated cAMP accumulation in neonatal rat kidney cells, and anti-sCT serum significantly reduced AP extract-induced cAMP accumulation. These results demonstrate that pit-CT is an important regulator of tonic PRL secretion in female rats and can potently inhibit PRL secretion even in the presence of dopamine.

Animals↗
PubMed1996

Renal effects of adrenomedullin in the rat.

We investigated the effects of a constant infusion of adrenomedullin (ADM) on renal hemodynamics and fluid electrolyte excretion in the rat. Following baseline measurements, eight rats received an intravenous infusion of 5 micrograms of rat ADM (167 ng/min) for 30 min at 10 microliters/min. Eight additional rats received 0.9% saline at 10 microliters/min instead of ADM. Renal function was measured during this period and for two consecutive 20-min periods following termination of the ADM or vehicle infusion. Mean arterial pressure decreased from a baseline of 113 +/- 3 to 102 +/- 1 mm Hg at 25 min of ADM infusion and returned towards control after the ADM infusion was terminated. This modest hypotensive effect was associated with an increase in heart rate from 366 +/- 10 to 384 +/- 9 bpm, which continued to remain elevated after the ADM infusion was stopped. Urinary sodium excretion increased from 348 +/- 57 to 813 +/- 172 nEq/min during ADM infusion and continued to increase to 1141 +/- 347 nEq/min after the infusion of ADM was terminated. Urinary potassium excretion increased from 1.94 +/- 0.22 to 2.75 +/- 0.24 microEq/min during ADM infusion. Urine flow tended to increase (P = 0.08) from 7.0 +/- 0.5 to 8.1 +/- 0.6 microliters/min during ADM infusion and continued to increase to 9.7 +/- 1.5 microliters/min after the infusion was stopped. Renal plasma flow increased from 3.22 +/- 0.22 to 3.82 +/- 0.20 ml/min/g kidney wt during ADM infusion and continued to increase to 4.14 +/- 0.22 ml/min/g kidney wt after the ADM infusion was stopped. Glomerular filtration rate averaged to 1.11 +/- 0.07 ml/min/g kidney wt during baseline and did not significantly change during or after ADM infusion. These results indicate that a constant infusion of adrenomedullin, at a dose that results in a minimal hypotensive effect increases renal plasma flow and urinary sodium excretion in the rat.

Adrenomedullin↗
PubMed1995

Opposing neuroendocrine actions of the natriuretic peptides: C-type and A-type natriuretic peptides do not interact with the same hypothalamic cells controlling prolactin secretion.

The two major members of the family of natriuretic peptides (NPs) in brain, A-type natriuretic peptide (ANP) and C-type natriuretic peptide (CNP) exert opposing actions on the neuroendocrine regulation of prolactin (PRL) secretion. We have targeted for compromise and destruction cells within the diencephalon which bear receptors for ANP (NRP-A receptors), CNP (NRP-B receptors), or both peptides (NPR-C receptors) using novel cytotoxin cell targeting methodology in order to determine if the neuroendocrine effects of these two peptides are exerted on similar cell systems. In animals pretreated with ANP conjugated to the cytotoxic A chain of ricin, central administration of a dose of ANP which is known to inhibit PRL secretion did not alter PRL levels in plasma; however, subsequent administration of CNP elicited the stimulation of PRL secretion. In rats pretreated with CNP-ricin A chain conjugate, a treatment we hypothesize targets for destruction CNP responsive cells, ANP injection did inhibit PRL secretion, while the stimulatory effect of CNP was absent. These results suggest that the neuroendocrine effects of these two natriuretic peptides on PRL secretion are expressed on different cellular elements of the hypothalamo-pituitary axis. Furthermore, they reveal that neither peptide acts directly on the tuberoinfundibular dopamine system since pretreatment with either cytotoxin conjugate failed to alter basal PRL levels. Thus ANP and CNP do not appear to express opposing actions on the same cell systems, suggesting the recruitment of each peptide individually by differing, unique stimuli for PRL release.

Animals↗
PubMed1995

Central oxytocin and ANP receptors mediate osmotic inhibition of salt appetite in rats.

These studies evaluated the involvement of central oxytocin (OT) and atrial natriuretic peptide (ANP) receptors in the osmotic inhibition of hypovolemia-induced salt appetite. Rats were pretreated centrally with the A chain of the cytotoxin ricin conjugated to OT (rAOT) or ANP (rAANP) to selectively inactivate cells bearing these respective receptors, or rats were pretreated with the unconjugated A chain (rA) as a control. Hypovolemia was induced with subcutaneous colloid injections, and rats then were given either 2 M mannitol, which raises plasma osmolality but lowers plasma sodium, or 1 M NaCl, which raises both. Hypertonic mannitol inhibited saline ingestion in rA-treated control rats but stimulated ingestion in rAOT- and rAANP-treated rats, whereas hypertonic NaCl blunted saline ingestion in rA- and rAOT-treated rats but stimulated ingestion in rAANP-treated rats. Angiotensin II-induced saline intake was similarly potentiated in rAOT- and rAANP-treated rats, indicating that this treatment also activates central inhibitory OT and ANP pathways. These data suggest that central ANP receptors mediate both Na(+)- and osmolality-induced inhibition of NaCl ingestion, whereas central OT receptors primarily mediate osmolality-induced inhibition of NaCl ingestion in rats.

Animals↗
PubMed1995

A novel vasoactive peptide, adrenomedullin, inhibits pituitary adrenocorticotropin release.

The potent hypotensive peptide, adrenomedullin (AdM), originally isolated from a human pheochromocytoma is present in a variety of rat and human tissues. We examined its potential effects in anterior pituitary gland, reasoning that it may be a feedback regulator of adrenocorticotropin (ACTH) secretion. Rat AdM11-50 inhibited basal ACTH secretion from dispersed, rat anterior pituitary cells in a significant, dose-related fashion (maximum inhibition at 10(-9) M). Rat AdM11-50 also inhibited, in a dose-related fashion, corticotropin releasing hormone (CRH)-stimulated ACTH secretion, but did not block the ability of CRH to stimulate cAMP accumulation in these cells. These findings suggest that in addition to peripheral actions in the vasculature and kidney, adrenomedullin may act within the anterior pituitary gland to control fluid and electrolyte homeostasis.

Adrenocorticotropic Hormone↗
PubMed1995

The novel vasoactive hormone, adrenomedullin, inhibits water drinking in the rat.

The novel hormone, adrenomedullin (AdM), which exerts potent hypotensive effects in the periphery and natriuretic actions in the kidney, was found to be antidipsogenic. Cerebroventricular injection of AdM (22, 44, and 88 pmol) resulted in a dose-related diminution of water drinking in response to subsequent central administration of 100 pmol angiotensin II. Additionally, 88 pmol AdM significantly inhibited the drinking response to overnight water deprivation and hyperosmotic challenge. No significant effects of AdM in the doses tested were observed on blood pressure, heart rate, or motor activity. These results suggest that this novel hormone can act within the nervous system to complement its peripheral actions on fluid and electrolyte homeostasis, independent of a central action on cardiovascular function or locomotion.

Adrenomedullin↗
PubMed1995

Oxytocin and the anterior pituitary gland.

Release of oxytocin into the vicinity of the long portal vessels connecting the hypothalamus with the anterior pituitary gland and the presence of short portal vessels connecting the posterior lobe to the anterior pituitary established the potential for the peptide to act in a neuroendocrine fashion controlling the release of one or several adenohypophyseal hormones. Indeed, oxytocin receptors are present in the gland and numerous trophic effects of the peptide have been described, some with apparent physiological relevance. Thus under defined physiologic conditions a participatory role for oxytocin in the physiologic regulation of at least two hormones, prolactin and adrenocorticotropin, has been evidenced and there is developing credence to the concept that oxytocin may indirectly control gonadotroph function as well. Most recently, novel technologies have identified subpopulations of oxytocin receptive cells within a given cell type in the anterior pituitary gland and the concept of a modulatory effect of the nonapeptide on primary regulatory events has arisen.

Adrenocorticotropic Hormone↗
PubMed1993

Central oxytocin inhibition of salt appetite in rats: evidence for differential sensing of plasma sodium and osmolality.

Sodium chloride ingestion is stimulated during conditions of sodium deficiency to maintain body fluid and electrolyte balance. Recent studies have indicated that salt appetite in rats is often inversely related to peripheral and central secretion of the hormone oxytocin (OT). We studied the potential role of central OT on salt and water ingestion by treating rats intracerebroventricularly with OT conjugated to the A chain of the plant cytotoxin ricin (rAOT) to produce a chronic selective inactivation of brain cells containing OT-receptive elements. The rats treated with rAOT and control rats treated with the ricin A chain alone were given 5-hr two-bottle (water and 0.5 M NaCl) drinking tests 30 min after they were made hyperosmolar by injections of hypertonic (2M) mannitol solution, which elevated plasma osmolality but reduced plasma Na+ concentration. In the control rats only water intake was stimulated in response to the induced hyperosmolality, but in the rAOT-treated rats hypertonic mannitol caused a robust salt appetite as well as thirst. Analogous results were obtained in rats treated with two different OT-receptor antagonists prior to induction of hyperosmolality with mannitol. In contrast to these results, when hyperosmolality was induced by administration of equivalently hypertonic (1M) NaCl, which elevated both plasma osmolality and plasma Na+ concentration, only water intake but not salt intake was stimulated in both control and OT-receptor antagonist-treated rats. When salt appetite was stimulated by the physiological stimulus of polyethylene glycol-induced hypovolemia, hypertonic mannitol similarly inhibited salt ingestion in control animals but not in rAOT-treated rats, whereas hypertonic NaCl inhibited subsequent salt ingestion in both groups. These results suggest that salt appetite is regulated by both Na(+)- and osmolality-sensing mechanisms in rats. In addition, they indicate that central OT likely mediates a significant component of osmolality-related inhibition of salt appetite but does not appear to be essential for Na(+)-related inhibition of this important homeostatic behavior.

Animals↗
PubMed1993

Antidipsogenic actions of endothelins are exerted via the endothelin-A receptor in the brain.

The receptor subtype mediating the antidipsogenic effects of the endothelins (ETs) was determined in conscious, unrestrained, normally hydrated rats. Intracerebroventricular injection of 6, 12, and 20 ng ET-2 resulted in a significant, dose-related inhibition of water drinking in response to subsequent injection of 100 pmol angiotensin II (ANG II). Pretreatment with 50 or 100 ng ET-B receptor agonist failed to alter the subsequent drinking response to ANG II. Drinking in response to ANG II was significantly accentuated in rats pretreated with 50, 100, and 200 ng of the selective ET-A receptor antagonist BQ-123. These data indicate that the antidipsogenic effects of the ETs are mediated via the ET-A receptor subtype and further suggest that endogenous ET plays a physiologically relevant role in the central nervous system control of fluid and electrolyte homeostasis.

Angiotensin II↗
PubMed1993

C-type natriuretic peptide mediates the hypothalamic actions of the natriuretic peptides to inhibit luteinizing hormone secretion.

Both A- and C-type natriuretic peptides (ANP and CNP, respectively) significantly reduce LH secretion when injected into the third cerebral ventricle of conscious rats. To establish which natriuretic peptide receptor subtype transduces these inhibitory messages, we have employed novel cytotoxin cell targeting techniques to selectively destroy cells in the hypothalamus that respond to ANP or CNP. Rats pretreated with ANP conjugated to the toxic A-chain of the plant cytotoxin ricin failed 1 week later to respond to central injection of ANP with the normal inhibition of LH secretion. These rats did, however, respond with significant inhibition of LH secretion to central injection of CNP. In fact, the LH inhibition observed after CNP injection was significantly greater than that expressed after similar injection of CNP in rats pretreated with unconjugated ricin A-chain (toxin control). Those control rats displayed significant reduction of LH levels in response to ANP injection as well. Plasma LH levels were not significantly affected by central administration of either ANP or CNP in rats pretreated with ricin A-chain conjugated to CNP. These results further demonstrate the power of this novel technology and provide positive evidence supporting our hypothesis that ANP exerts its LH-inhibiting effect by displacing endogenous CNP from clearance receptors within the brain. This endogenous CNP, then, like exogenously applied CNP, activates the guanyl cyclase-B receptors on cells, which are part of the network controlling the release of LHRH.

Animals↗
PubMed1992

The endothelin-A receptor subtype transduces the effects of the endothelins in the anterior pituitary gland.

All members of the mammalian endothelin family of peptides exert significant effects on prolactin and luteinizing hormone release from dispersed anterior pituitary cells in vitro. The rank order of potency for the prolactin inhibiting effects of the endothelins is ET-1 = ET-2 much less than ET-3. This suggests an involvement of the ET-A receptor subtype. The selective ET-A receptor antagonist BQ-123 antagonized the effects of the ETs in a competitive fashion with pA2 values of 6.1 (ET-1), 5.7 (ET-2) and 6.4 (ET-3), when added simultaneously with the ETs. This suggests the involvement of the ET-A receptor subtype in the actions of the ETs within the anterior pituitary gland.

Animals↗