Analysis of carotid chemoreceptor responses to substance P analogue in anaesthetized cats

Abstract

Analogues of Substance P (SP) have been shown to act as SP receptor antagonists in various physiological systems. We have previously shown that the carotid body sensory response to hypoxia could be attenuated by d-Pro 2- d-Trp 7,9-SP (DPDT-SP) and suggested that SP may be important for chemoreception. In the absence of detailed characterization of the antagonistic effects of DPDT-SP, the role of SP in carotid body chemoreception remains uncertain. The present study was undertaken to analyze the effects of DPDT-SP on carotid body activity in anaesthetized cats ( n = 18). Intra-carotid infusion of DPDT-SP antagonized SP-induced chemoreceptor stimulation. 90% blockade of SP responses was obtained at infusion rates of 15 μg/kg per min of DPDT-SP for 15 min. By contrast, infusions of either saline (controls) or at doses below 10 μg/kg per min had no effect on SP responses. The doses that effectively antagonized SP excitation (i.e., 15 μg/kg per min) also blocked or markedly attenuated the chemoreceptor responses to hypoxia, without affecting the carotid body stimulation caused by nicotine. The effects of DPDT-SP were associated with significant reduction in baseline activity in normoxia. The antagonistic effects were reversible after terminating the infusion of DPDT-SP. Increasing the dose to 25 μg/kg per min, however, abolished the carotid body excitation by any of the stimuli tested (i.e., SP, hypoxia and nicotine), indicating that at higher doses DPDT-SP is non-selective. These results demonstrate that DPDT-SP given in adequate doses to block SP response also attenuates or abolishes the carotid body excitation by hypoxia. The antagonistic effects are reversible and appear to be selective. These observations, taken together with the previous studies, support the notion that SP is coupled to hypoxic response of the cat carotid body.