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Pharmacological characterization of the phosphoinositide second messenger system in the rabbit kidney

Thesis/Dissertation ·
OSTI ID:7152114
The cellular response to hormones and neurotransmitters is a result of receptor activation of a second messenger system to initiate the intracellular cascade. In several tissues, such as brain and liver, one of the second messenger systems involves the hydrolysis of phosphoinositides (PIs) for the formation of inositol phosphate and diacylglycerol as the intracellular messengers. In the present study, they examined the effect of various agents on the hydrolysis of PIs in the rabbit kidney. In the kidney, the effect of the various hormones and neurotransmitters was region specific. Hydrolysis of PIs was stimulated in the inner medulla by (arg{sup 8})-vasopressin, angiotensin II, and atriopeptin I, and in the outer medulla by histamine, adenosine, and secretin. Only carbachol was able to stimulate the hydrolysis of PIs in both the inner and outer medulla. None of the substances tested were able to stimulate this response in the cortex. The following agents did not have an effect in any of the three zones of the kidney: norepinephrine, dopamine, atriopeptins II, and III. They have directly demonstrated the presence of a high affinity saturable binding site on inner medullary collecting duct (IMCD) cells with studies of binding characteristics of the radiolabelled muscarinic antagonist, 1-quinuclidinyl (phenyl-4-{sup 3}H) benzilate (({sup 3}H)QNB). The K{sub d} of 0.27 nM and the B{sub max} of 27.5 fmol/mg protein were determined from Scatchard analysis of the saturation data. In summary, they have demonstrated that cholinergic muscarinic receptors are present in the rabbit kidney, specifically in the IMCD cells. These receptors, which are coupled to the hydrolysis of phosphoinositides, may be involved in the vasodilatory and/or diuretic effects of cholinergic agents.
Research Organization:
Florida Univ., Gainesville, FL (USA)
OSTI ID:
7152114
Country of Publication:
United States
Language:
English