PubMed Health⌕ Search

Biomedical subjects

Martin W Wessendorf

Publications and source records attributed to Martin W Wessendorf.

5 recordsLinked to original sources
PubMed2004

Serotonergic and nonserotonergic dorsal raphe neurons are pharmacologically and electrophysiologically heterogeneous.

The dorsal raphe nucleus (DRN) projects serotonergic axons throughout the brain and is involved in a variety of physiological functions. However, it also includes a large population of cells that contain other neurotransmitters. To clarify the physiological and pharmacological differences between the serotonergic and nonserotonergic neurons of the DRN, their postsynaptic responses to 5-hydroxytryptamine (5-HT, serotonin) and to selective activation of 5-HT1A or 5-HT2A/C receptors and their action potential characteristics were determined using in vitro patch-clamp recordings. The slices containing these neurons were then immunostained for tryptophan hydroxylase (TPH), a marker of serotonergic neurons. It was found that subpopulations of both serotonergic and nonserotonergic neurons responded to 5-HT with outward (i.e., inhibitory) and inward (i.e., excitatory) currents, responded to both 5-HT1A and 5-HT2A/C receptor activation with outward and inward currents, respectively, and displayed overlapping action potential characteristics. These findings suggest that serotonergic and nonserotonergic neurons in the DRN are both heterogeneous with respect to their individual pharmacological and electrophysiological characteristics. The findings also suggest that the activity of the different populations of DRN neurons will display heterogeneous changes when the serotonergic tone in the DRN is altered by neurological disorders or by drug treatment.

Action Potentials↗
PubMed2004

Expression of MOR1C-like mu-opioid receptor mRNA in rats.

The reverse transcriptase-polymerase chain reaction (RT-PCR) was used to clone a cDNA fragment of a putative G-protein-coupled receptor from rat brain total RNA. Nucleotide sequencing of this cDNA fragment showed it to be homologous to that of the mu-opioid receptor splice variant MOR(1C) from mice. We used the cDNA to make an RNA probe for a ribonuclease protection assay (RPA). The results from the RPA showed a protected fragment of the size expected for MOR(1C) mRNA, as well as other RNase-protected fragments that may indicate the existence of other MOR1 transcripts. We then used the RNA probe for in situ hybridization (ISH) experiments. We detected strong autoradiographic labeling over much of the rat telencephalon, diencephalon, mesencephalon, cerebellum, spinal cord, and dorsal root ganglia. These findings suggest that MOR(1C), and possibly other MOR1 splice variants, are important components of the system by which the actions of opioids are transduced.

Amino Acid Sequence↗
PubMed2002

Rostral ventromedial medulla neurons that project to the spinal cord express multiple opioid receptor phenotypes.

The rostral ventromedial medulla (RVM) forms part of a descending pathway that modulates nociceptive neurotransmission at the level of the spinal cord dorsal horn. However, the involvement of descending RVM systems in opioid analgesia are a matter of some debate. In the present study, patch-clamp recordings of RVM neurons were made from rats that had received retrograde tracer injections into the spinal cord. More than 90% of identified spinally projecting RVM neurons responded to opioid agonists. Of these neurons, 53% responded only to the mu-opioid agonist D-Ala2, N-Me-Phe4, Gly-ol5 enkephalin, 14% responded only to the kappa-opioid agonist U-69593, and another group responded to both mu and kappa opioids (23%). In unidentified RVM neurons, a larger proportion of neurons responded only to mu opioids (75%), with smaller proportions of kappa- (4%) and mu/kappa-opioid (13%) responders. These RVM slices were then immunostained for tryptophan hydroxylase (TPH), a marker of serotonergic neurons. Forty-percent of spinally projecting neurons and 11% of unidentified neurons were TPH positive. Of the TPH-positive spinally projecting neurons, there were similar proportions of mu- (33%), kappa- (25%), and mu/kappa-opioid (33%) responders. Most of the TPH-negative spinally projecting neurons were mu-opioid responders (67%). These findings indicate that functional opioid receptor subtypes exist on spinally projecting serotonergic and nonserotonergic RVM neurons. The proportions of mu- and kappa-opioid receptors expressed differ between serotonergic and nonserotonergic neurons and between retrogradely labeled and unlabeled RVM neurons. We conclude that important roles exist for both serotonergic and nonserotonergic RVM neurons in the mediation of opioid effects.

Animals↗
PubMed2002

Ultrastructure of endomorphin-1 immunoreactivity in the rat dorsal pontine tegmentum: evidence for preferential targeting of peptidergic neurons in Barrington's nucleus rather than catecholaminergic neurons in the peri-locus coeruleus.

Endomorphins are opioid tetrapeptides that have high affinity and selectivity for mu-opioid receptors (muORs). Light microscopic studies have shown that endomorphin-1 (EM-1) -containing fibers are distributed within the brainstem dorsal pontine tegmentum. Here, immunoelectron microscopy was conducted in the rat brainstem to identify potential cellular interactions between EM-1 and tyrosine hydroxylase (TH) -labeled cellular profiles in the locus coeruleus (LC) and peri-LC, an area known to contain extensive noradrenergic dendrites of LC neurons. Furthermore, sections through the rostral dorsal pons, from colchicine-treated rats, were processed for EM-1 and corticotropin releasing factor (CRF), a neuropeptide known to be present in neurons of Barrington's nucleus. EM-1 immunoreactivity was identified in unmyelinated axons, axon terminals, and occasionally in cellular profiles resembling glial processes. Within axon terminals, peroxidase labeling for EM-1 was enriched in large dense core vesicles. In sections processed for EM-1 and TH, approximately 10% of EM-1-containing axon terminals (n=269) targeted dendrites that exhibited immunogold-silver labeling for TH. In contrast, approximately 30% of EM-1-labeled axon terminals analyzed (n = 180) targeted CRF-containing somata and dendrites in Barrington's nucleus. Taken together, these data indicate that the modulation of nociceptive and autonomic function as well as stress and arousal responses attributed to EM-1 in the central nervous system may arise, in part, from direct actions on catecholaminergic neurons in the peri-LC. However, the increased frequency with which EM-1 axon terminals form synapses with CRF-containing profiles in Barrington's nucleus suggests a novel role for EM-1 in the modulation of functions associated with Barrington's nucleus neurons such as micturition control and pelvic visceral function.

Animals↗