Medullary raphe: a new site for vagally mediated stimulation of gastric motility in cats

Abstract

Thyrotropin-releasing hormone (TRH) is clearly implicated in the control of gastric function via interactions in the dorsal motor nucleus of the vagus (DMV) of the cat. The source of the TRH innervation of the DMV is important to determine because this region could be of importance in control of gastric function. TRH-immunoreactive (ir) neurons are located in the raphe obscurus (Ro), raphe pallidus (Rp), and raphe magnus (Rm). Retrograde tracer applied to the DMV resulted in the most numerous labeled neurons in the caudal Ro and Rp in the same region where TRH-ir neurons are located. To address the question whether DMV-projecting neurons in the raphe subnuclei play a role in control of gastric motility, the following experiments were performed in alpha-chloralose-anesthetized cats while recording pyloric motility and blood pressure. Microinjection of a cell body excitant L-glutamate (44-200 nl, 0.5 M) into the caudal Ro and Rp in 15 experiments produced significant increases in pyloric minute motility index (MMI) of 4.9 +/- 1.5 (from 1.6 +/- 0.7 preinjection to 6.5 +/- 1.8 postinjection, P less than 0.05). Mean blood pressure (MBP) decreased significantly in these animals by 12 +/- 7 mmHg (from 100 +/- 6 to 88 +/- 8 mmHg, P less than 0.05). Saline microinjection in the same sites in seven cases resulted in no significant change in pyloric MMI (-1.0 +/- 0.8) or MBP (-4 +/- 11 mmHg). In five of these experiments, a second microinjection of L-glutamate (132-240 nl) was performed into the caudal Ro and Rp after spinal cord transection. This resulted in a significant increase in pyloric MMI of 3.3 +/- 0.9 (from 1.0 +/- 0.5 preinjection to 4.3 +/- 1.1 postinjection, P less than 0.05) but no change in MBP (+1 +/- 1 mmHg). Bilateral vagotomy resulted in the abrupt cessation of the pyloric response to caudal Ro and Rp stimulation. Microinjection of L-glutamate into the rostral Rp and caudal Rm in nine experiments resulted in no significant changes in pyloric MMI (-0.4 +/- 0.8) or MBP (-10 +/- 11 mmHg). These data indicate that a population of neurons in the caudal raphe nuclei, which may contain TRH, project to the DMV. In addition, excitation of these neurons causes an increase in gastric motility that is not caused by inhibition of sympathetic outflow to the gut but rather by excitation of vagal neurons in the DMV.

Comparison of the effects of IVth ventricular administration of some tryptamine analogues with those of 8‐OH‐DPAT on autonomic outflow in the anaesthetized cat

“…This is somewhat surprising since the tryptamine analogues DP-5-CT and 5-CT have comparable effects to 8-OH-DPAT on central sympathetic drive, especially renal nerve activity, which it is possible (see above) to attribute to activation of 5-HTIA receptors. Further it is interesting that none of the agonists used in the present study, even 8-OH-DPAT, increased the excitability of other central parasympathetic motoneurones, such as those that control the airways and gastric motility, although central 5-HT pathways have been implicated in the control of gastric motility (Hornby et al, 1990 (Gillis et al, 1989). The present data only demonstrated that the fall in blood pressure was of a similar magnitude but the changes in the various variables which were causing the fall in blood pressure differed, suggesting that the relationship between 5-HTlA and 5-HT2 receptors in control of sympathetic outflow is not simply opposing at the level of the brainstem.…”

Opposing effects on blood pressure following the activation of metabotropic and ionotropic glutamate receptors in raphe obscurus in the anaesthetized rat

“…When both agonist and antagonist were injected, the latter preceded the former by 10 rain. Data are means _+ SE (CNQX 6-Cyano-7-nitroquinoxaline-2,3-dione, 2-APV D,L-amino-phosphono-valeric acid, MK801 (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d~cyclohepten-5,10-imine hydrogen malate, M CPG ( + )-e-methyl-4-carboxy phenyl-glycine) Treatment Dose (nmol/rat) n A arterial blood pressure L-glu 3 6 20 _+ 5.4 N M D A 5 6 24 _+ 7.2 t-ACPD 28 6 -16 _+ 4.2 CNQX + L-glu 0.4 + 3 6 21 _+ 5.9 2-APV + L-glu 5 + 3 6 3 + 2.6** 2-APV + N M D A 5 + 5 6 1 _+ 1.2"* MK 801 + L-glu 0.9 + 3 6 -3 + 2.5** MK 801 + N M D A 0.9 + 5 6 4 + 2.2** M C P G + L-glu 0.05 + 3 6 34 _4-4.1" M C P G + t-ACPD 0.05 + 28 6 -3 _+ 1.8"* either pressor or depressor responses (Hornby et al 1990;Dreteler et al 1991), in the present experiments the administrations of L-glu into this nucleus caused only increases in blood pressure. Our results have characterized the glutamate receptor subtypes involved in the pressor response induced by the administration of L-glu into the nucleus raphe obscurus.…”

“…Physiological studies have indicated the involvement of caudal raphe neurones in cardiovascular control (Hornby et al 1990;Dreteler et al 1991;Lovick 1992;Wang and Lovick 1993;Gilbey et al 1994) and many studies have demonstrated that the administration of glutamate into the caudal raphe nuclei elicits pressor effects (Minson et al 1987;Hornby et al 1990;Dreteler et al 1991) although the glutamate receptor subtypes involved have not been established. The aim of the study was to characterize the glutamate receptor subtypes [-ionotropic or metabotropic (Collingridge and Lester 1989;Barnard and Henley 1990;Baskys 1992;Schoepp and Conn 1993)] involved in eliciting the blood pressure effects originating in the raphe obscurus following the injection of excitatory amino acid agonists.…”

Behavioral correlates of the activity of serotonergic and non-serotonergic neurons in caudal raphe nuclei

“…First, the major projections of these nuclei are directed at the somatic motor/premotor and the visceral motor-secretory/premotor-secretory nuclei of the brainstem and spinal cord. Well-known target structures are the trigeminal motor nucleus (1), facial nucleus (2), nucleus ambiguus (3), hypoglossus nucleus (4,5), the ventral horn of the spinal cord (6)(7)(8), the medial medul-lary reticular formation (9), the ventral respiratory group (10), the red nucleus (11), the dorsal motor nucleus of the vagus (12), the intermediolateral cell column of the spinal cord (13)(14)(15) and the rostral ventrolateral medulla and surrounding regions (9,16,17). At least part of the axons terminate directly in motoneurons (7,18) or preganglionic autonomic neurons (15).…”

“…Second, increased NRP or NRO activity induced by electrical or chemical stimulation facilitates trigeminal motoneurons (18), facilitates or depresses phrenic motoneurons (19)(20)(21), facilitates lumbar motoneurons (22,23), facilitates motor and secretory gastric preganglionic neurons in the dorsal motor nucleus of the vagus (12,24), and facilitates or depresses sympathetic preganglionic neurons to the heart and vessels (25,26).…”