Detail of "148498-78-6"

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Circulating adrenomedullin does not regulate systemic blood pressure but increases plasma prolactin after intravenous infusion in humans: a pharmacokinetic study

Circulating adrenomedullin does not regulate systemic blood pressure but increases plasma prolactin after intravenous infusion in humans: a pharmacokinetic study. Meeran, Karim; O'Shea, Donal; Upton, Paul D.; Small, Caroline J.; Ghatei, Mohammad A.; Byfield, Peter H.; Bloom, Stephen r. (Division Endocrinology Metabolism, Hammersmith Hospital, London W12 0NN, UK). Journal of Clinical Endocrinology and Metabolism, 82(1), 95-100 (English) 1997 Endocrine Society. CODEN: JCEMAZ. ISSN: 0021-972X. DOCUMENT TYPE: Journal CA Section: 2 (Mammalian Hormones) Adrenomedullin has been proposed to be a circulating hormone regulating systemic and pulmonary blood pressure. A potential therapeutic role in the management of pulmonary hypertension has been suggested based on animal studies, but the pharmacokinetics and pharmacodynamics in human subjects have not been studied. The authors have infused adrenomedullin into volunteers at 3.2 pmol/kg×min, which more than quadrupled (52 pmol/L) normal circulating concns. At this dose no change in heart rate or blood pressure was noted.Some commonly used reagents like 148498-78-6 and 9002-62-4 are used in this experiment. When infused at 13.4 pmol/kg×min to achieve a concn. over 40 times normal circulating levels (448 pmol/L), there was a significant fall in diastolic blood pressure from 69 to 53 mm Hg and a significant increase in pulse rate from 57 to 95 beats/min. Circulating PRL concns. rose from 197 to 372 IU/L. No effect was seen on ACTH, TSH, FSH, LH, or cortisol. When the infusion was discontinued, baseline pulse and blood pressure were reestablished after 20 min. Adrenomedullin has a MCR of 27.4 mL/kg×min, with a circulating half life of 22 min and an apparent vol. of distribution of 880 mL/kg. Column chromatog. of plasma taken during infusion and decay of adrenomedullin showed no evidence of the prodn. of addnl. mol. forms. These results are consistent with a peptide that is markedly tissue bound. Plasma adrenomedullin concns. were increased in patients with renal impairment (14.1 pmol/L) compared to those in healthy volunteers (8.1 pmol/L), with a good correlation (r = 0.86) between circulating adrenomedullin and plasma creatinine. The circulating concn. of adrenomedullin necessary to affect blood pressure greatly exceeds that obsd. in healthy volunteers and in patients with a range of pathol. conditions. Thus, adrenomedullin may be a paracrine regulator of vascular smooth muscle in humans. .

Adrenomedullin-(22-52) antagonizes vasodilator responses to CGRP but not adrenomedullin in the cat

Adrenomedullin-(22-52) antagonizes vasodilator responses to CGRP but not adrenomedullin in the cat. Champion, Hunter C.; Santiago, Jose A.; Murphy, William A. 148498-78-6 and 119911-68-1 are also occured in this study.; Coy, David H.; Kadowitz, Philip J. (Dep. Pharmacology Med., Tulane Univ. Sch. Med., New Orleans, LA 70112, USA). American Journal of Physiology, 272(1, Pt. 2), R234-R242 (English) 1997 American Physiological Society. CODEN: AJPHAP. ISSN: 0002-9513. DOCUMENT TYPE: Journal CA Section: 2 (Mammalian Hormones) The effects of adrenomedullin (ADM)-(22-52), a putative ADM receptor antagonist, on vasodilator responses to ADM and the structurally related peptide, calcitonin gene-related peptide (CGRP), were investigated in the hindlimb vascular bed of the cat under const.-flow conditions. ADM-(22-52) had no significant effect on hindlimb perfusion pressure when injected in doses up to 120 nmol; after administration of ADM-(22-52), vasodilator responses to ADM were unchanged, whereas vasodilator responses to CGRP were inhibited. The inhibitory effects of ADM-(22-52) on responses to CGRP were selective and reversible and were similar to the inhibitory effects of the CGRP antagonist CGRP-(8-37). Hindlimb vasodilator responses to CGRP and to ADM were increased in duration by the cAMP phosphodiesterase inhibitor rolipram but were not altered by inhibitors of cGMP phosphodiesterase, nitric oxide synthetase, K+-ATP channels, the cyclooxygenase pathway, or the adrenergic nervous system. These results demonstrate that ADM-(22-52) is a selective CGRP receptor antagonist in the hindlimb vascular bed of the cat. The present data suggest that vasodilator responses to CGRP and ADM are mediated by different receptors but that these peptides dilate the hindlimb vascular bed of the cat by a similar cAMP-dependent mechanism. .