Activation of central nervous system cholecystokinin receptors stimulates respiration in the cat

RA Gillis, JA Quest, FD Pagani, JD Souza, AM Da Silva, RT Jensen, TQ Garvey and P Hamosh

Cholecystokinin-octapeptide (CCK-OP) was injected into the lateral brain ventricle of chloralose-anesthetized cats while monitoring pulmonary ventilation, mean blood pressure (BP) and heart rate (HR). Initial values for respiratory minute volume, BP and HR were 436 +/- 32 ml/min, 126 +/- 8 mm Hg and 204 +/- 9 beats/min, respectively. CCK-OP in doses of 8.8 x 10(-13) to 8.8 x 10(-10) M (i.e., 1 to 1000 ng) increased respiratory minute volume by +56 +/- 18 ml/min to +370 +/- 73 ml/min, respectively. This response was due to an increase in tidal volume (P less than .05) with no effect on respiratory rate. Most of these doses increased BP and HR (P less than .05). These responses were mimicked when CCK-OP was administered into and restricted to the lateral and 3rd ventricles, whereas no significant responses occurred with administration into the 4th ventricle. The highest dose of CCK-OP, when given i.v., produced no significant effects. Central nervous system injections (lateral ventricle) of CCK-OP in deafferented animals also produced respiratory and cardiovascular stimulation, but higher doses were required. Central nervous system injections of comparable doses of desulfated CCK-OP or pentagastrin had no effect on respiratory minute volume, BP or HR. Proglumide (0.8 and 8.0 mg), a specific CCK receptor antagonist, prevented both respiratory and cardiovascular effects induced by CCK-OP. These doses of proglumide exerted no antagonism of CO2-induced respiratory stimulation. These data suggest that a specific receptor reacting with CCK-OP may be important for the control of respiration.

Volume 224, Issue 2, pp. 408-414, 02/01/1983
Copyright © 1983 by American Society for Pharmacology and Experimental Therapeutics

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