Effects of Β‐endorphin, Vasoactive Intestinal Polypeptide and Cholecystokinin Octapeptide on Cat Carotid Chemoreceptor Activity

Abstract

The effects of beta-endorphin, vasoactive intestinal polypeptide (VIP) and cholecystokinin octapeptide (CCK-8) on carotid chemoreceptor activity have been investigated in cats anaesthetized with pentobarbitone. Spontaneous chemoreceptor discharge was decreased by intracarotid injection of beta-endorphin and by low doses of VIP, whereas it was increased by CCK-8 and higher doses of VIP, these effects being relatively long-lasting and often associated with changes in systemic blood pressure. The chemoexcitation evoked by acetylcholine and sodium cyanide was reduced during intracarotid infusion of any of the three peptides studied, and that caused by CO2-saturated Locke solution was reduced by beta-endorphin, largely unaltered by VIP and variably affected by CCK-8. The inhibitory effect of beta-endorphin was greatly reduced by naloxone, implying that it probably involved actions at naloxone-sensitive opiate receptors in the carotid body. Substance P was unable to overcome the chemoinhibitory effect of methionine enkephalin. Possible functions of polypeptides in the carotid body are discussed.

Characterization of opioid receptors in the cat carotid body involved in chemosensory depression in vivo

“…There was no tendency for opioids to cause marked chemoexcitation following administration of either ICI 154129 or ICI 174864 in our study. In some experiments a slight variable dose-related increase in discharge was obtained with ethylketocyclazocine and dynorphin (1-8), much the same as that observed with P-endorphin following naloxone (McQueen & Ribeiro, 1981b). It is not clear whether these very variable excitatory effects result from actions mediated via opioid receptors, or are non-specific actions ofopioids administered in high doses.…”

l-Cysteine ethyl ester reverses the deleterious effects of morphine on, arterial blood–gas chemistry in tracheotomized rats

“…Systemic opioids also depress ventilation in animals by mechanisms, including central- (Campbell et al, 1995) and vagal afferent-mediated (Kaczy ska and Szereda-Przestaszewska, 2005) depression of ventilatory drive; skeletal muscle rigidity in the chest-wall and abdomen (Seamman, 1983; Niedhart et al, 1989; Bowdle, 1998); increases in pulmonary airway resistance (Willette et al, 1983); and increases in upper airway resistance via closure of the larynx (Willette et al, 1982, 1987; Bennett et al, 1997). Moreover, agonist-induced activation of central and peripheral opioid receptors blunt the hypoxic ventilatory response (see Zhang et al, 2009), and opioids such morphine and fentanyl inhibit carotid body chemoafferent activity and depress the responses of these afferents to hypoxic and hypercapnic challenges (McQueen and Rubeiro, 1980, 1981; Zimpfer et al, 1983; Kirby and McQueen, 1986; Mayer et al, 1989). Opioids including morphine also negatively affect ventilation-perfusion in the lungs of rabbits (Shafford and Schadt, 2008), pigs (Hannon and Bossone, 1991), dogs (Copland et al, 1987) and rats (Ling et al, 1985; Szikszay et al, 1986).…”

Histopathology of carotid body in heroin addiction. Possible chemosensitive impairment

“…dorsal and ventral respiratory regions) 9 . The effects of opiates on the carotid body have been studied only in functional experimental studies on animals, which revealed that methionine‐enkephalin, β‐endorphin and morphine decrease spontaneous chemoreceptor discharge 10–12 . Moreover, the carotid chemoreceptor response to hypoxia is enhanced by intravenous injection of naloxone, thus supporting the role of endogenous opiates in basal suppression of the ventilatory effects of peripheral chemoreceptors 12,13 …”