Daniel R. Kapusta, PhD
Research Interests
Research focuses on understanding the role of opioid (mu- and kappa-) and opioid-like peptides (nociceptin/orphanin FQ) in the regulation of cardiovascular and renal function. A major focus is to determine how opioid/nociceptin systems interact with other hormones, neurotransmitters and the renal nerves in the regulation of renal tubular sodium and water handling during normal and pathological conditions (e.g. hypertension, congestive heart failure, cirrhosis with ascites). These investigations employ techniques for measurement of changes in cardiovascular and renal function and direct recording of renal nerve activity. From the knowledge obtained from these investigations, we are attempting to develop novel water diuretics for the clinical management of fluid retaining states.
Selected Publications
Gottlieb, H.B., Varner, K.J., Kenigs, V.A., and Kapusta, D.R.: Differential cardiovascular and renal responses produced by microinjection of the kappa opioid, U-50488H, into subregions of the paraventricular nucleus. J. Pharmacol. Exp. Therap., 312:678-685, 2005.
Kapusta, D.R., Burmeister, M., Calo’, G., et. al., V.A.: Functional selectivity of nociceptin/orphanin FQ peptide receptor partial agonists on cardiovascular and renal function. J. Pharmacol. Exp. Therap., 314:643-651, 2005.
Kapusta, D.R., Thorkildsen, C., Kenigs, V.A., Meier, E., Vinge, M.M., Quist, C., and Petersen, J.S.: Pharmacodynamic characterization of ZP120, a novel functionally selective NOP receptor partial agonist with sodium-potassium-sparing aquaretic activity. J. Pharmacol. Exp. Therap., 314:652-660, 2005.
Calo’, G., Guerrini, R., Rizzi, A., Salvadori, S., Burmeister, M., Kapusta, D.R., Lambert, D.R., and Regoli, D.: UFP-101, a peptide antagonist for the N/OFQ receptor. CNS Drug Rev., 11:97-112, 2005.
Gottlieb, H. and Kapusta, D.R.: Endogenous central kappa opioid systems enhance renal sympathetic nerve activity and contribute to maximal urinary sodium retention during hypotonic saline volume. Am. J. Physiol., 289:R1289-1296, 2005.
Larsen, B.D., Petersen, J.S., Harlow, K., Kapusta, D.R.: A diuretic nociceptin derivative. US patent # 09/882,291.
Krowicki, Z.B. and Kapusta, D.R.: Tonic nociceptinergic inputs to neurons in the hypothalamic paraventricular nucleus contribute to sympathetic vasomotor tone and water and electrolyte homeostasis in conscious rats.J. Pharmacol. Exp. Therap., 317:446-53, 2006.
Rizzi, A., Spagnolo, B., Wainford, R.D., Fischetti, C., Guerrini, R., Marzola, G., Baldisserotto, A., Salvadori, S., Regoli, D., Kapusta, D.R., Calo, G.: In vitro and in vivo studies on UFP-112, a novel potent and long lasting agonist selective for the N/OFQ receptor. Peptides, 28:1240-51, 2007.
Burmeister, M.A. and Kapusta, D.R.: Centrally administered nociceptin/orphanin FQ (N/OFQ) evokes bradycardia, hypotension, and diuresis in mice via activation of central N/OFQ peptide receptors. J. Pharmacol. Exp. Therap., 322:324-31, 2007.
Wainford, R.A., Kurtz, K., Kapusta, D.R: Central G-alpha subunit protein mediated control of cardiovascular function, urine output and vasopressin (AVP) secretion in conscious Sprague-Dawley rats. Am. J. Physiol., 295:R535-R542, 2008.
Burmeister, M.A. and Kapusta, D.R.: Nociceptin/orphanin FQ (N/OFQ)-evoked bradycardia, hypotension and diuresis are absent in N/OFQ peptide (NOP) receptor knockout (NOP-/-) mice. J. Pharmacol. Exp. Therap., 326:897-904, 2008.
Wainford, R.D., Kristine Kurtz, and Kapusta, D.R: Central G-alpha subunit protein mediated control of cardiovascular function, urine output and vasopressin (AVP) secretion in conscious Sprague-Dawley rats. Am. J. Physiol., 295:R535-R542, 2008.
Guggilam A, Patel KP, Haque M, Ebenezer PJ, Kapusta DR, Francis J.: Cytokine blockade attenuates sympathoexcitation in heart failure: cross-talk between nNOS, AT-1R and cytokines in the hypothalamic paraventricular nucleus. Eur. J. Heart Fail. 10:625-634, 2008.
Wainford, R.D. and Kapusta, D.R.: Chronic high-NaCl intake prolongs the cardiorenal responses to central N/OFQ and produces regional changes in the endogenous brain NOP receptor system. Am. J. Physiol.296:R280-R288, 2009.