Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “parathyroid hormone”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,711 records · Page 95Linked to original sources
PubMed1995

Parathyroid hormone stimulates electrogenic sodium transport in A6 cells.

The effects of parathyroid hormone (PTH) on sodium homeostasis in the distal tubule are not well defined. Using A6 cells as a model for distal tubular epithelium we measured equivalent short circuit current (leq), as an estimate of net sodium transport. We found that PTH increased leq in a dose-dependent manner. DDA, an agent which inhibits adenylate cyclase, decreased PTH-activated sodium transport, suggesting a role for cAMP elevation in PTH effects. Moreover, addition of Rp-cAMP, an inhibitor of cAMP-dependent protein kinase, partially blocked the PTH-stimulated leq. PTH also elicited a sustained increase in [Ca2+]i in A6 cells. This elevation in [Ca2+]i was abolished by removal of calcium from the extracellular medium, suggesting the involvement of calcium influx pathways. In fact, addition of the calcium channel blocker nitrendipine to PTH-stimulated leq partially blocked PTH-activated sodium transport. Taken together these data demonstrate that PTH stimulates electrogenic sodium transport in A6 cells and that this effect may be mediated through a rise in both intracellular calcium and cellular cAMP.

Adenylyl Cyclase Inhibitors↗
PubMed1996

Effect of parathyroid hormone on rat skeletal muscle in vivo.

The secondary hyperparathyroidism of chronic renal failure has been implicated in the pathogenesis of metabolic abnormalities in skeletal muscle. We studied the muscle metabolism in a model of hyperparathyroidism (Wistar rats injected with parathyroid hormone or saline for 4 days). 31P magnetic resonance spectroscopy allowed measurements of the concentration of cytosolic metabolically active inorganic phosphate [Pi] at rest and the rates of oxidative and anaerobic adenosine triphosphate turnover during exercise and recovery. Parathyroid hormone caused significant reductions in plasma [Pi] and intracellular [Pi], but had no effect upon oxidative or glycogenolytic adenosine triphosphate turnover.

Adenosine Triphosphate↗
PubMed1980

Parathyroid hormone stimulates bone resorption via a Na-Ca exchange mechanism.

Parathyroid hormone (PTH) stimulates the release of calcium from bone and is thought to initiate its action by a direct effect on the plasma membrane of bone cells. Although specific membrane receptors for PTH have not yet been identified in bone, they have been characterized in kidney, and PTH does stimulate production of cyclic AMP in bone. However, the mechanism by which PTH causes the release of Ca from bone is not understood. We have determined that several agents that alter ion transport across biological membranes inhibit PTH-stimulated bone resorption in vitro. These agents include ouabain, veratridine and certain monovalent cation ionophores, which transport monovalent cations selectively. The inhibition of bone resorption is dose dependent and reversible within the first 24 h of treatment. All these compounds would be expected to increase intracellular sodium concentration in bone cells. Also, we find that decreasing the extracellular Na+ concentration prevents PTH-stimulated resorption. Therefore, we propose that PTH acts on bone to stimulate Ca release by means of a Na-Ca exchange mechanism. Decreasing the Na gradient across the bone cell plasma membrane would prevent the Na-Ca exchange and thus inhibit the physiological response to PTH.

Animals↗
PubMed1986

Cyclic AMP and the vascular action of parathyroid hormone.

The involvement of tissue cAMP in the vasodilating action of parathyroid hormone (PTH) was investigated. The bovine active fragment bPTH-(1-34) was used in all studies. In anesthetized dogs, theophylline, a phosphodiesterase inhibitor, potentiated the hypotensive action of bPTH-(1-34) at the dose of 1 microgram/kg. The potentiation was related to the dose of theophylline infused. In an in vitro rat tail artery helical strip assay, dibutyryl cAMP produced dose-related relaxation in arginine vasopressin (AVP) constricted blood vessels. bPTH-(1-34) also produced dose-related relaxation in the tail artery constricted by AVP. In the presence of isobutylmethylxanthine, another phosphodiesterase inhibitor, the bPTH-(1-34) dose--response curve was shifted to the left, indicating potentiation. Imidazole, which has phosphodiesterase stimulating activity, significantly decreased the in vitro vasorelaxing effect of bPTH-(1-34). In addition, bPTH-(1-34) increased significantly the rat tail artery cAMP content. b-PTH-(1-34) oxidized with hydrogen peroxide lost its vasorelaxing activity and was also ineffective in increasing the tail artery cAMP content. All these data strongly suggest that cAMP may be involved in eliciting the vasorelaxing action of bPTH-(1-34).

1-Methyl-3-isobutylxanthine↗
PubMed1987

A 6-hour human parathyroid hormone (1-34) infusion protocol: studies in normal and hypoparathyroid subjects.

Parathyroid hormone (PTH)-resistant states are usually diagnosed by the failure of an acute PTH injection to elicit a rise in urinary cAMP and phosphate or, less commonly, by the failure of repeated PTH injections to raise serum calcium. We have established a 6 hour infusion of human PTH (1-34) which identifies PTH-resistant hypoparathyroid subjects on the basis of serum 1,25-dihydroxyvitamin D (1,25(OH)2D) and calcium responses. 1,25-Dihydroxyvitamin D levels increased by at least 58 pmol/liter and serum calcium by at least 0.1 mmol/liter in PTH-responsive hypoparathyroid subjects (n = 6), whereas in pseudohypoparathyroid subjects (n = 5) these levels rose by less than 22 pmol/liter and 0.06 mmol/liter respectively. The responsiveness of urinary phosphate excretion, expressed as the renal threshold phosphate concentration (TmPO4/GFR), to PTH also clearly separated the pseudohypoparathyroid patients from the other subjects. Differences in urinary calcium responses were observed though this parameter was less reliable in the identification of individual PTH-resistant or PTH-sensitive hypoparathyroid patients. Nephrogenous cAMP did not discriminate between groups when this protocol was used. This test has the potential to facilitate and extend the classification of PTH-resistant states.

Adult↗
PubMed2003

Relationship between plasma level of parathyroid hormone and carboxymethyllysine in hemodialyzed patients--does it exist?

AIMS: Both parathyroid hormone and advanced glycated end products (AGEs) are uremic toxins. The present study aimed to examine the likely interrelationship between these compounds. METHODS: Seventy-four hemodialyzed patients (41 female, 33 male; mean age 47 +/- 2 years, mean duration on hemodialysis 36 +/- 6 months) were enrolled in this study. In all subjects, the body mass index (BMI) was calculated and total lean mass (TLM) and total fat mass (TFM) were assessed by dual X-ray absorptiometry. Blood samples for estimation of plasma calcium, phosphorus, carboxymethyl lysine (as marker of AGEs) and PTH-1-84 were obtained after overnight fasting, before subsequent hemodialysis session. RESULTS: BMI, TFM and TLM were 23.6 +/- 0.5 kg/m2, 16.3 +/- 1.0 kg and 46.3 +/- 1.1 kg, respectively. PTH plasma level (223 +/- 32 pg/ml) and plasma CML (1,837 +/- 84 ng/ml) were markedly elevated as compared with reference values. A significant positive correlation was found between TLM and CML levels (tau = 0.225; p = 0.04) and between plasma PTH and CML levels (tau = 0.224; p = 0.04). CONCLUSION: It seems likely that PTH and AGEs are interrelated. The pathophysiological relevance of this finding in the pathogenesis of uremic toxicity remains to be elucidated.

Body Mass Index↗
PubMed1990

Preparation and characterization of [N alpha-(4-azido-2-nitrophenyl)Ala1,Tyr36]-parathyroid hormone related peptide (1-36)amide: a high-affinity, partial agonist having high cross-linking efficiency with its receptor on ROS 17/2.8 cells.

The synthesis, purification, and structural analysis of the major compounds resulting from photoderivatization of [Tyr36]-parathyroid hormone related peptide (1-36)amide [[Tyr36]PTHrP(1-36)amide] are described. The reaction of the synthetic peptide with 4-fluoro-3-nitrophenyl azide under nonaqueous conditions yields three major products (peaks D-1, D-2, and G), which were purified to homogeneity by reverse-phase high-performance liquid chromatography. Subsequent amino acid analysis showed that the peptides of peaks D-1 and G each lack one lysine residue, while the peptide in peak D-2 lacks one alanine residue, suggesting that these residues are chemically modified by photoderivatization. Sequence analysis of the photoderivatized peptides revealed that compounds D-1 and G were derivatized on Lys13 and Lys11, respectively. Compound D-2 was N-blocked, indicating that this compound is derivatized on the alpha-amino function of Ala1. Both Lys residues of D-2 were quantitatively recovered upon sequencing after digestion with endoproteinase Glu-C. Compounds D-2 and G had apparent KdS of 1 X 10(-9) M and 0.6 X 10(-9) M, respectively, for their receptors on ROS 17/2.8 cells, which are identical with or similar to that of the underivatized [Tyr36]PTHrP(1-36)amide. Compound G had the same adenylate cyclase stimulating potency as the underivatized, synthetic [Tyr36]PTHrP(1-36)amide, whereas compound D-2 was only a partial agonist, having about 25% of the maximal cAMP production. Compound D-1, which is modified on Lys13, retained only 2-4% of its receptor binding affinity and biological activity relative to that of its parent compound.(ABSTRACT TRUNCATED AT 250 WORDS)

Affinity Labels↗
PubMed1988

Comparison of the effects of dopamine and fenoldopam, a selective dopamine-1 agonist, on parathyroid hormone release in man.

Dopamine has been reported to transiently increase parathyroid hormone (PTH) secretion in man; however, the mechanism is unclear. To test the hypothesis that selective dopamine-1 receptor (DA1) stimulation increases PTH secretion, we compared the effects of fenoldopam, a novel selective DA1 receptor agonist, as well as dopamine on serum PTH secretion and total serum calcium concentration in seven normal human subjects. Dopamine was infused at 1 and 3 micrograms/kg/min, each for 10 minutes, and 5 micrograms/kg/min for 25 min. Fenoldopam was infused at 0.1 and 0.3 micrograms/kg/min, each for 10 min. and thereafter at 0.5 micrograms/kg/min for 25 min. The infusions were given at least 1 week apart. Blood samples for PTH, calcium and dopamine or fenoldopam concentrations were drawn prior to and at the 25th minute of each drug infusion. PTH concentrations increased in all subjects at the 25th minute of dopamine but not fenoldopam infusion. Serum calcium was not significantly affected. The plasma concentrations of both dopamine (83.6 +/- 7.1 ng/ml) and fenoldopam (13.0 +/- 3.4 ng/ml) were in the range known to cause equivalent DA1 receptor stimulation. Since dopamine but not fenoldopam increased PTH secretion in man, we conclude that selective DA1 receptor stimulation alone does not increase PTH release and the effects of dopamine must be mediated through some other mechanism.

Adolescent↗
PubMed1988

Parathyroid hormone impairs extrarenal potassium tolerance in the rat.

The effect of parathyroid hormone (PTH) on the extrarenal disposition of an acute potassium load was examined in acutely nephrectomized rats infused with KCl (0.75 meq.kg-1.h-1 for 90 min) alone or in combination with 8-10 U.kg-1.min-1 PTH, with serial monitoring of plasma potassium every 10 min. The rise in plasma potassium concentration (delta PK) in the PTH group was higher than control. PTH was then administered along with KCl to two groups of nephrectomized and acutely thyroparathyroidectomized (TPTX) rats in doses of 1 and 0.25 U.kg-1.min-1 for 90 min. delta PK with PTH in both groups was higher than TPTX control (P less than 0.01). The two higher doses of PTH resulted in a decrease in mean arterial pressure from their respective controls. A similar reduction in arterial pressure in three groups of nephrectomized rats by administration of hydralazine or nitroprusside or by acute blood loss did not change delta PK subsequent to potassium infusion from that in control rats. Furthermore, the lowest dose of PTH did not lower arterial pressure from its respective control. Therefore, hypotension is not a cause for the PTH-induced potassium intolerance. Serum levels of insulin, aldosterone, catecholamines, calcium, plasma HCO3 concentration, and pH were not different in PTH-infused vs. respective control rats. These data suggest that PTH impairs extrarenal potassium disposal in the rat. The effect of PTH may relate to enhanced calcium entry into cells.

Animals↗
PubMed1998

Development of a scintillation proximity assay for high-throughput measurement of intact parathyroid hormone.

A simple, high-throughput scintillation proximity assay (SPA) for parathyroid hormone (1-84) (PTH) has been developed. Fifteen commercially available N-terminal and six C-terminal anti-PTH antibodies were evaluated for detection of human PTH(1-84). Two C-terminal antibodies (CR1073M and 10-P55) gave the most consistent results. Using one of these antibodies (10-P55), an assay was developed with a sensitivity of 4 pg/ml for human and rat PTH(1-84). Porcine PTH(1-84) was not detectable. The intra-assay and inter-assay coefficients of variation for a 467 pg/ml sample were 6. 1 and 6.5%, respectively, and for a 21 pg/ml sample, 6.2 and 4.4%. Human PTH(1-34), while not detected in the assay, interfered with the detection of PTH(1-84). Smaller fragments [for example, human PTH(3-34)] and a C-terminal PTH fragment [PTH(53-84)] did not interfere in the assay. The procedure gave 106-110% recovery of human PTH(1-84) spiked into samples. Immunoreactive PTH concentrations in serum of rats administered EGTA were determined by SPA and by a commercially available PTH immunoassay. There was a good correlation between the two assays with significant increases in serum immunoreactive PTH concentrations at 15 and 30 min after EGTA injection and a rapid decrease to baseline values by 60 min. The SPA gives a high-throughput method for simply and accurately determining PTH(1-84) concentrations in serum.

Animals↗
PubMed2006

Parathyroid hormone stimulates endothelial expression of atherosclerotic parameters through protein kinase pathways.

Parathyroid hormone (PTH), the major systemic calcium-regulating hormone, has been linked to uremic vascular changes. Considering the possible deleterious action of PTH on vascular structures, it seemed logical to evaluate the impact of PTH on the receptor of advanced glycation end products (RAGE) and interleukin 6 (IL-6) mRNA and protein expression, taking into account that such parameters might be involved in the pathogenesis of vascular calcification, atherosclerosis, and/or arteriolosclerosis. Human umbilical vein cord endothelial cells (HUVEC) were stimulated for 24 h with 10(-12)-10(-10) mol/l PTH. The mRNA expression of RAGE and IL-6 was established by reverse transcriptase/PCR techniques. RAGE protein levels were determined by Western blot and IL-6 secretion was measured by ELISA. The pathways by which PTH may have an effect on HUVEC functions were evaluated. PTH (10(-11)-10(-10)mol/l) significantly increased RAGE mRNA and protein expression. PTH also significantly increased IL-6 mRNA expression without changes at protein levels. The addition of protein kinase (PKC or PKA) inhibitors or nitric oxide (NO) synthase inhibitors significantly reduced the RAGE and IL-6 mRNA expression and the RAGE protein expression. PTH stimulates the mRNA expressions of RAGE and IL-6 and the protein expression of RAGE. These stimulatory effects are probably through PKC and PKA pathways and are also NO dependent. Such data may explain the possible impact of PTH on the atherosclerotic and arteriosclerotic progression.

Atherosclerosis↗
PubMed1979

Immunological properties of synthetic human parathyroid hormone 53--84 fragment.

The immunological properties of a synthetic peptide comprising the carboxyl-terminal 53--84 region of human parathyroid hormone (PTH) have been studied. The immunoreactivity of the synthetic human PTH-(53--84) peptide paralleled that of a 53--84 fragment of the native human hormone prepared by enzymic digestion, in both a standard radioimmunoassay, which was not region-specific, and also a radioimmunoassay specific for the carboxyl-terminal region of PTH. However, in both types of radioimmunoassay the synthetic human PTH-(53--84) peptide was four to five times more reactive than the native human PTH-(53--84) fragment.

Hormones↗
PubMed2001

Parathyroid hormone increases the expression level of matrix metalloproteinase-13 in vivo.

Parathyroid hormone (PTH) increases serum calcium (Ca) by enhancing bone resorption and renal Ca reabsorption. However, detailed mechanisms of enhanced bone resorption by PTH remain to be elucidated. Although PTH has been shown to increase the expression level of osteoblastic matrix metalloproteinase (MMP)-13 in vitro, only limited results are available regarding the in vivo regulation of MMP expression. In the present study, we have examined expression levels of MMPs in PTH-infused rats. Infusion of 1.5 or 2.0 nmol/kg/day rat PTH(1-34) for 3 days resulted in a dose-dependent increase in serum Ca. PTH infusion also decreased serum phosphate levels and increased urinary excretion of Ca and phosphate. Infusion of PTH for 7 days resulted in less severe hypercalcemia and hypophosphatemia. Urinary Ca and phosphate excretion in rats infused for 7 days was less than that in rats infused for 3 days. Northern blot analysis showed that PTH infusion increased the expression level of MMP-13 in calvaria, although it did not affect MMP-2 expression. Furthermore, the time-course and severity of hypercalcemia and hypercalciuria correlated with the expression level of MMP-13. In situ hybridization also showed that PTH infusion increased the expression level of MMP-13 in femora. These results indicate that PTH enhances MMP-13 expression in vivo and suggest that PTH stimulates bone resorption at least partly by enhancing MMP-13 expression.

Animals↗
PubMed2002

The murine gene encoding parathyroid hormone: genomic organization, nucleotide sequence and transcriptional regulation.

The type 1 parathyroid hormone receptor (PTHR1) binds, with equal affinity, two ligands with distinct biological functions: PTH, the major peptide hormone controlling calcium homeostasis, and the paracrine factor, PTH-related peptide (PTHrP), a local regulator of cellular proliferation and differentiation. To clarify the complexity of possible interactions between two distinct ligands, PTH and PTHrP, and their common receptor in the intact organism, and to identify as yet unrecognized roles for PTH in normal physiology, we have cloned and characterized the structural organization, nucleotide sequence and transcriptional regulation of the murine gene encoding PTH. One recombinant clone isolated from a mouse genomic library contained 14 kb of DNA, encompassing the entire Pth gene. The transcriptional unit spans 3.2 kb of genomic DNA and, analogous to the human PTH gene, it is interrupted by two introns. The deduced mRNA encodes the 115-amino acid precursor, preproPTH. Comparison of the murine preproPTH sequence with other mammalian forms of the protein shows it to be highly conserved and to share limited structural similarity to PTHrP at the amino-terminal region, a domain critical for binding and activation of their common receptor. Putative binding motifs for the transcription factors sex-determining region Y gene product, transcriptional repressor CDP, hepatic nuclear factor 3beta, GATA-binding factor 1, glucocorticoid receptor, SRY-related high mobility group box protein 5 and cAMP response element binding protein were identified in the 5' flanking region of the Pth gene. When placed upstream of a reporter gene, these sequences failed to confer transcriptional regulation in response to 1,25(OH)(2) vitamin D(3), but responded positively to the addition of isoproterenol and forskolin. Mutational analysis identified a cAMP-response element in the Pth promoter.

Amino Acid Sequence↗
PubMed1980

Characterization of the dopamine-responsive adenylate cyclase of bovine parathyroid cells and its relationship to parathyroid hormone secretion.

To investigate further the mechanism of dopamine (DA)-stimulated and parathyroid hormone (PTH) secretion, we have identified and studied DA-sensitive adenylate cyclase in a particulate preparation of osmotically lysed dispersed bovine parathyroid cells. Adenylate cyclase was responsive to DA at concentrations as low as 0.3 microM, and the maximal stimulation in the presence of GTP was 2- to 4-fold that of activity with GTP alone. (-)Propranolol (1 microM) abolished the stimulation by (-)isoproterenol but did not inhibit the DA-stimulated adenylate cyclase, whereas alpha-flupenthixol (1 microM) inhibited DA stimulation but not that of (-)isoproterenol. The dopaminergic agonists epinine and 6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene were nearly as effective as DA in stimulating the enzyme, while apomorphine displayed partial agonist activity. The dopaminergic antagonists chlorpromazine, fluphenazine, and haloperidol inhibited the DA-stimulated adenylate cyclase. There was a close correspondence between the Ka values for DA and the Ki values of the dopaminergic antagonists for particulate adenylate cyclase activity, cellular cAMP accumulation, and PTH release. These results indicate that DA-stimulated cAMP accumulation and PTH release are mediated through specific activation of a DA receptor linked to adenylate cyclase.

Adenylyl Cyclases↗
PubMed2000

The expression of the nuclear matrix proteins NuMA, topoisomerase II-alpha, and -beta in bone and osseous cell culture: regulation by parathyroid hormone.

Bone cells undergo changes in cell structure during phenotypic development. Parathyroid hormone (PTH) induces a change in osteoblast shape, a determinant of collagen expression. We hypothesize that alterations in bone cell shape reflect and direct gene expression as governed, in part, by nuclear organization. In this study, we determined whether the expression of nuclear matrix proteins that mediate nuclear architecture, NuMA, topoisomerase II (topo II)-alpha, and -beta, were altered during osteoblast development and response to PTH in vivo. NuMA forms an interphase nuclear scaffold in some cells, the absence of which may accommodate alterations in nuclear organization necessary for specific functions. Topo II enzymes are expressed in bone cells; the alpha-isoform is specific to proliferating cells. We used immunohistochemistry and flow cytometry to determine whether NuMA is expressed in the primary spongiosa of the rat metaphyseal femur and whether expression of NuMA, topo II-alpha, and II-beta changes during osteoblast development or with PTH treatment. NuMA and topo II-beta were expressed in marrow cells, osteoblasts, osteocytes, and chondrocytes. These proteins were not detected in osteoclasts in vivo, but were observed in cultured cells. Bone marrow cells expressed topo II-alpha. All three proteins were expressed in cultures of rat osteoblast-like UMR-106 cells. PTH treatment downregulated the number of topo II-alpha-immunopositive cells, correlated with a decrease in S-phase cells, in both bone tissue and cell culture. We conclude that, in vivo, nuclear matrix composition is altered during bone cell development and that anabolic doses of PTH attenuate the proliferative capacity of osteogenic cells, in part, by targeting topo II-alpha expression.

Animals↗
PubMed2005

Parathyroid hormone induces the NR4A family of nuclear orphan receptors in vivo.

Parathyroid hormone (PTH) has both anabolic and catabolic effects on bone metabolism, although the molecular mechanisms mediating these effects are largely unknown. Among the transcription factors induced by PTH in osteoblasts are the nerve growth factor-inducible factor B (NR4A; NGFI-B) family of orphan nuclear receptors: Nurr1, Nur77, and NOR-1. PTH induces NR4A members through the cAMP-protein kinase A (PKA) pathway in vitro. We report here that PTH rapidly and transiently induced expression of all three NR4A genes in PTH-target tissues in vivo. In calvaria, long bones, and kidneys, NR4A induction was maximal 0.5-1 h after a single intraperitoneal (i.p.) injection of 80 microg/kg PTH. Nur77 demonstrated the highest expression, followed, in order, by Nurr1 and NOR-1. In calvaria and long bone, PTH-induced expression of each NR4A gene was detectable at 10 microg/kg i.p. with maximum induction at 40-80 microg/kg. PTH (3-34) did not induce NR4A mRNA levels in calvaria, long bone, and kidney in vivo, confirming our in vitro results that NR4A genes are induced primarily through the cAMP-PKA pathway. The magnitude of PTH-induced NR4A expression was comparable in vivo and in vitro. However, NR4A mRNA levels peaked and returned to baseline faster in vivo. Both in vivo and in vitro, PTH induced NR4A pre-mRNA levels suggesting that induction of these genes is, at least in part, through activation of mRNA synthesis. The in vivo induction of the NR4A family members by PTH suggests their involvement in, at least some, PTH-induced changes in bone metabolism.

Animals↗
PubMed2006

Comparison of hypotensive response following intravenous injection of parathyroid hormone 1-84 and 1-34 in conscious rats.

Activation of parathyroid hormone 1 (PTH-1) receptors on vascular smooth muscle cells causes relaxation and decreases blood pressure in rats and humans. However, when PTH(1-84) and PTH(1-34) were injected in anesthetized rats, PTH(1-34) produced a greater decrease in blood pressure. This study quantified the dose-response relationship of the hypotensive response to intravenously injected PTH(1-84) and PTH(1-34) in conscious rats and assessed the role that the C-terminal region of PTH(1-84) played in the differences. Mean arterial pressure (MAP) decreased rapidly following injection of both peptides (0-100 nmol/kg) and reached a nadir at 1-2 minutes before increasing at a rate that was dose- and time-dependent. PTH(1-34) produced a greater hypotensive effect than PTH(1-84) at most doses tested and was significantly different from PTH(1-84) at 1-10 nmol/kg. The greatest difference in MAP decrease between PTH(1-84) and PTH(1-34) (24 and 35 mm Hg, respectively) occurred at 10 nmol/kg. Median effective dose (ED50) values for PTH(1-84) and PTH(1-34) were significantly different (5.9 and 1.3 nmol/kg, respectively). The C-terminal PTH fragments PTH(7-84), PTH(39-84), and PTH(53-84) did not affect MAP when injected alone (10 nmol/kg), nor did they influence the hypotensive response when given at a 10-fold molar excess in combination with PTH(1-84) or PTH(1-34) (1.4 nmol/kg). In conclusion, PTH(1-84) is a less potent but, because it induced the same maximum response, not a less efficacious hypotensive agent than PTH(1-34) when administered by bolus intravenous injection in conscious rats. We found no evidence to support the concept that the C-terminal region of PTH is responsible for this difference in potency.

Animals↗