Depressor and bradycardic responses to microinjections of endomorphin-2 into the NTS are mediated via ionotropic glutamate receptors

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology Vol. 56; no. 4; pp. R715 - R728
• Main Authors: KASAMATSU, Ken, CHITRAVANSHI, Vineet C, SAPRU, Hreday N
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Physiological Society 01.10.2004
• Subjects: Biological and medical sciences; Blood pressure; Cardiac dysrhythmias; Cardiology; Cardiology. Vascular system; Circulatory system; Drug therapy; Fundamental and applied biological sciences. Psychology; Heart; Medical sciences; Motor control and motor pathways. Reflexes. Control centers of vegetative functions. Vestibular system and equilibration; Neurons; Vertebrates: nervous system and sense organs; Ionotropic receptor; Cardiovascular control; Arrhythmia; Rat; opioid peptides; Central nervous system; Cardiovascular disease; Glutamate receptor; Encephalon; Heart disease; Arterial pressure; Antagonist; depressor responses; Sulfonamide; Endomorphin; Rodentia; Excitability disorder; Solitary nucleus; Heart rate; Vertebrata; Bradycardia; Mammalia; Microinjection; Animal; Excitatory aminoacid; Neurotransmitter; Hemodynamics; NMDA receptor
• ISSN: 0363-6119; 1522-1490

The presence of endomorphin-like immunoreactivity has been reported in the nucleus tractus solitarius (NTS). It was hypothesized that endomorphins may play a role in cardiovascular regulation in the medial subnucleus of the NTS (mNTS). Endomorphin-2 (E-2, 0.1-4 mmol/l) was microinjected (100 nl) into the mNTS of urethane-anesthetized, artificially ventilated, adult male Wistar rats. E-2 (0.2 mmol/l) elicited decreases in mean arterial pressure (40 +/- 3.5 mmHg) and heart rate (50 +/- 7.0 beats/min). These responses were blocked by prior microinjections of naloxonazine (1 mmol/l) into the mNTS. Responses to microinjections of E-2 into the mNTS were abolished by prior combined microinjections of d-2-amino-7-phosphonoheptanoic acid (an NMDA receptor antagonist, 5 mmol/l) and 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide disodium (a non-NMDA receptor antagonist, 2 mmol/l) into the mNTS. These results were confirmed by extracellular neuronal recordings. Blockade of GABA receptors in the mNTS by prior combined microinjections of gabazine (a GABAA receptor antagonist, 2 mmol/l) and 2-hydroxysaclofen (a GABAB receptor antagonist, 100 mmol/l) also blocked the responses to E-2. It was concluded that 1) the depressor and bradycardic responses to microinjections of E-2 into the mNTS are mediated via micro 1-opioid receptors as well as ionotropic glutamate receptors, 2) GABAergic neurons in the mNTS, which may inhibit the release of glutamate from nerve terminals, are inhibited by E-2 via micro 1-opioid receptors, and 3) disinhibition caused by the inhibition of GABAergic neurons by E-2 may result in an increase in the glutamate release from nerve terminals, which, in turn, may elicit depressor and bradycardic responses. [PUBLICATION ABSTRACT]