Chemistry: natural resins or derivatives; peptides or proteins; – Peptides of 3 to 100 amino acid residues – 25 or more amino acid residues in defined sequence
Patent
1995-02-24
1998-04-14
Tsang, Cecilia J.
Chemistry: natural resins or derivatives; peptides or proteins;
Peptides of 3 to 100 amino acid residues
25 or more amino acid residues in defined sequence
530325, 530326, 530327, 530328, 530329, 530333, 514 2, 514 7, C07K 704
Patent
active
057392749
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
This invention relates to the identification, characterization and synthesis of an active component of parathyroid hypertensive factor which comprises a polypeptide linked to a phosphoglyceride (sometimes referred to as phospholipid). The component exhibits activities substantially similar to parathyroid hypertensive factor and therefore is indicated in the control of extracellular calcium uptake, and is related to hypertension and some other diseases in mammals. Methods for screening patients for the presence of the circulating factor using antibodies against the component are described. Antagonists of the parathyroid hypertensive factor component have been developed and the use of such antagonists in methods of treating patients with diseases which involve intracellular calcium elevation are also described.
BACKGROUND OF THE INVENTION
Hypertension is generally defined as the elevation of the systolic and/or diastolic arterial blood pressure above a nominal value of 140/90 mm Hg. Diseases associated with hypertension include arteriosclerosis, hypertensive renal failure, stroke, congestive heart failure and myocardial infarction. Although numerous methods of treatment have been found to be effective in the reduction of arterial blood pressure, the etiology of essential hypertension remains essentially unknown. A genetic predisposition to hypertension is generally accepted, but the number of different drugs which have been found effective in the treatment of hypertension, and the fact that these drugs seem to operate by eliciting different pharmacological responses, suggests that there may be different primary causes for essential hypertension.
A number of studies have suggested that one or more circulating factors may et al., A Hypertensive Substance Found in the Blood of Spontaneously Hypertensive Rats; Life Sci. 1984; 34:1521-1528; Dahl et al., Humoral Transmission of Hypertension: Evidence from Parabiosis; Circ. Res. 1969; 24/25 (Suppl. I):21-23; Greenberg et al., Evidence for Circulating Factors as a Cause of Venous Hypertrophy in Spontaneously Hypertensive Rats; Am. J. Physiol. 1981; 241:H421-H430; Tobian et al., A Circulating Humoral Pressor Agent in Dahl S Rats with Salt Hypertension; Clin. Sci. 1979; 57:345s-347s; Zidek et al., Humoral Factors in the Pathogenesis of Primary Hypertension; Klin. Wochenschr. 1985; 63 (Suppl. II) D:94-96; Hirata et al., Hypertension Producing Factor in the Serum of Hypertensive Dahl Salt-Sensitive Rats; Hypertension 1984; 6:709-716!. For example, in parabiosis and cross-circulation experiments, an increase in blood pressure could be induced in normotensive animals by exposure to blood from hypertensive animals. The subcutaneous injection of erythrocyte-associated factor obtained from spontaneously hypertensive rats (SHR) has been shown to induce hypertension in normotensive Wistar-Kyoto (WKY) rats and an increase in blood pressure can be induced in normotensive, salt insensitive Dahl rats by injection of serum from hypertensive, salt-sensitive Dahl rats.
There have also been reports of circulating factors in both hypertensive Banos et al., Two Factors Associated with Increased Uptake of Calcium in Platelets from Essential Hypertensive Patients; Clin. Exp. Hypertens. 1987; 9:1515-1530; Zidek et al., Effect of Plasma from Hypertensive Subjects on Ca Transport in Permeabilized Human Neutrophils; Clin. Sci. 1988; 74:53-56; Linder et al., Effects of a Circulating Factor in Patients with Essential Hypertension on Intracellular Free Calcium in Normal Platelets; N. Eng. J. Med. 1987; 316:509-513; Bruschi et al., Cytoplasmic Free Ca is Increased in the Platelets of Spontaneously Hypertensive Rats and Essential Hypertensive Patients; Clin. Sci. 1985; 68:179-184; Wright et al., Stimulation of Aortic Tissue Calcium Uptake by an Extract of Spontaneously Hypertensive Rat Erythrocytes Possessing Hypertensive Properties; Can. J. Physiol. Pharmacol. 1986; 64:1515-1520!. Since vascular tone is influenced by the level of intracellular calcium, it would seem rea
REFERENCES:
patent: 5554728 (1996-09-01), Basava et al.
Benishin et al., "Purification of parathyroid hypertensive fctor from plasma of spontaneously hypertensive rats", Proc. Natl. Acad. Sci. USA, vol. 88, pp. 6372-9376, 1991.
Rudinger, Peptide Hormones, (ed. Parsons, J.A.), Baltimore, University Park Press, pp. 1-7, 1976.
Benishin Christina G.
Jie Shan
Lewanczuk Richard Z.
Pang Peter K. T.
CV Technologies Inc.
Gupta Anish
Tsang Cecilia J.
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